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1.
Hum Mov Sci ; 92: 103150, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37776752

ABSTRACT

Expert players in throwing sports may reduce the variability of projectile arrival position by systematically relating release parameters (e.g., release position, velocity, and angular velocity of the projectile). Reducing the variability of the projectile arrival position is often believed to increase the success rate of throwing task, but it may not be always true. Here, we experimentally illustrate that the systematic relationship between release parameters that reduce the variability of the ball arrival position may not increase the number of hitting trials during a throwing task. Furthermore, we demonstrate that the role of the release parameters in increasing successful trials can vary depending on the target size. Each participant threw balls at two different-sized targets (small and large target conditions). Additionally, they alternately threw balls with overhead and sidearm throwing for both the small and large targets. Our results showed that the release position and velocity in the left-right direction reduced the variability of the ball arrival position and increased the successful trials in the small target condition. In the large target condition, the two release parameters reduced the variability of the ball arrival position, but they did not increase the successful trials. Consequently, reducing the variability of the ball arrival position did not always equate to an increase in successful trials, as it depended on the target size. These findings indicate that the role of the release parameters in increasing hitting trials is not constant but varies depending on the condition of the motor task.


Subject(s)
Sports , Humans , Biomechanical Phenomena
2.
J Appl Biomech ; 39(3): 169-178, 2023 Jun 01.
Article in English | MEDLINE | ID: mdl-37142403

ABSTRACT

In sports situations, players may be required to throw at different speeds. The question of how skilled players throw the ball accurately to the desired location under different speed conditions is of interest to biomechanics researchers. Previous research suggested that throwers use different types of joint coordination. However, joint coordination with a change in throwing speed has not been studied. Here, we show the effects of changes in throwing speed on joint coordination during accurate overhead throwing. Participants were seated on a low chair with their trunk fixed and threw a baseball aimed at a target under 2 different speed conditions (slow and fast). In the slow condition, the elbow flexion/extension angle coordinated with other joint angles and angular velocities to reduce the variability of the vertical hand velocity. In the fast condition, the shoulder internal/external rotation angle and the shoulder horizontal flexion/extension angular velocity coordinated with other joint angles and angular velocities to reduce the variability of the vertical hand velocity. These results showed that joint coordination differed with changes in throwing speed, indicating that joint coordination is not always fixed, but may differ depending on the task constraints, such as throwing speed.


Subject(s)
Baseball , Elbow Joint , Shoulder Joint , Humans , Shoulder , Elbow , Upper Extremity , Biomechanical Phenomena
3.
Front Sports Act Living ; 5: 1092520, 2023.
Article in English | MEDLINE | ID: mdl-37090818

ABSTRACT

It is widely acknowledged that understanding the physical mechanics of the flight trajectories of four-seam fastballs and breaking balls is crucial for players and coaches to enhance pitching performance. The characteristics of the flight trajectories of four-seam fastballs and breaking balls have been revealed; however, the relationship between them has not been examined. Here, we show the characteristics of the flight trajectory of breaking balls from the four-seam fastballs. We found that the direction of the deviation of the curveballs could be generally predicted from that of the four-seam fastballs. We also found that the limits of the deviation of the sliders can be determined from the direction of the deviation of the four-seam fastball. This study revealed the deviation of the breaking ball from the four-seam fastballs, which clearly showed the differences in the characteristics between curveballs and sliders. This study moved forward with the description of the physical properties of each pitch type and allowed us to obtain valuable insights and practical implications.

4.
J Neurophysiol ; 127(4): 1171-1184, 2022 04 01.
Article in English | MEDLINE | ID: mdl-35320021

ABSTRACT

Humans can move objects to target positions out of their reach with certain accuracy by throwing or hitting them with tools. However, the outcome-the final object position-after the same movement varies due to various internal and external factors. Therefore, to improve outcome accuracy, humans correct their movements in the following trial as necessary by estimating the relationship between movement and visual outcome (visuomotor map). In the present study, we compared participants' error-correction behaviors to visual errors under three conditions, wherein the relationship between joystick movement direction and cursor projection direction on the monitor covertly differed. This allowed us to examine whether the error-correction behavior changed depending on the visuomotor map. Moreover, to determine whether participants maintain the visuomotor map regardless of the visual error size (cursor projection) and proprioceptive errors (joystick movement), we for the first time focused on whether temporary visual errors deviating from the conventional relationship between joystick movement direction and cursor projection direction (i.e., visual perturbation) are ignored. The visual information was occasionally perturbed in two ways to create a situation wherein the visual error was larger or smaller than the proprioceptive error. We found that participants changed their error-correction behaviors according to the conditions and could ignore visual perturbations. This suggests that humans can be implicitly aware of differences in visuomotor maps and adapt accordingly to visual errors.NEW & NOTEWORTHY We found that participants changed their error-correction behaviors according to the conditions and could ignore visual perturbations. This suggests that humans can be implicitly aware of differences in visuomotor maps and adapt accordingly to visual errors. These findings provide suggestions for how to notice and adapt our movements to the environment and our own dynamically changing conditions, to perform accurate movements consistently.


Subject(s)
Goals , Psychomotor Performance , Adaptation, Physiological , Humans , Movement , Proprioception , Visual Perception
5.
Front Sports Act Living ; 3: 753062, 2021.
Article in English | MEDLINE | ID: mdl-34723181

ABSTRACT

Coordination is a multidisciplinary concept in human movement science, particularly in the field of biomechanics and motor control. However, the term is not used synonymously by researchers and has substantially different meanings depending on the studies. Therefore, it is necessary to clarify the meaning of coordination to avoid confusion. The meaning of coordination in motor control from computational and ecological perspectives has been clarified, and the meanings differed between them. However, in biomechanics, each study has defined the meaning of the term and the meanings are diverse, and no study has attempted to bring together the diversity of the meanings of the term. Therefore, the purpose of this study is to provide a summary of the different meanings of coordination across the theoretical landscape and clarify the meaning of coordination in biomechanics. We showed that in biomechanics, coordination generally means the relation between elements that act toward the achievement of a motor task, which we call biomechanical coordination. We also showed that the term coordination used in computational and ecological perspectives has two different meanings, respectively. Each one had some similarities with biomechanical coordination. The findings of this study lead to an accurate understanding of the concept of coordination, which would help researchers formulate their empirical arguments for coordination in a more transparent manner. It would allow for accurate interpretation of data and theory development. By comprehensively providing multiple perspectives on coordination, this study intends to promote coordination studies in biomechanics.

6.
Hum Mov Sci ; 77: 102799, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33892401

ABSTRACT

It is known that coordination between joint movements is crucial for the achievement of motor tasks and has been studied extensively. Especially, in sports biomechanics, researchers are interested in determining which joint movements are coordinated to achieve a motor task. However, this issue cannot be easily addressed with the methods employed in previous studies. Therefore, we aimed to propose a method for identifying joint coordination. Subsequently, we examined which joint movements were coordinated using accurate overhead throwing, which required reduction in vertical hand velocity variability. Fourteen baseball players participated by attempting throwing using a motion capture system. The index of coordination for each joint movement and the effect of deviation of one joint movement on vertical hand velocity were quantified. Our results showed that the shoulder internal/external rotation angle (θ1-IE) and the other joint movements or the shoulder horizontal flexion/extension angular velocity (ω1-FE) and the other joint movements were coordinated. These results could be explained by the fact that the effects of the deviation of the shoulder internal rotation angle (θ1-I) and shoulder horizontal flexion angular velocity (ω1-F) on vertical hand velocity were larger than those of the other joint movements. This meant that it was necessary to cancel the deviations of θ1-IE and ω1-FE by the other joint movements. These findings indicate that the method proposed in this study enables the identification of which joint movements are coordinated in multiple degrees of freedom.


Subject(s)
Baseball , Biomechanical Phenomena , Movement , Range of Motion, Articular , Shoulder Joint/physiology , Shoulder/physiology , Adult , Athletes , Hand , Humans , Joints/physiology , Male , Rotation , Sports , Wrist/physiology , Young Adult
7.
Article in English | MEDLINE | ID: mdl-33345042

ABSTRACT

There is a need within human movement sciences for a markerless motion capture system, which is easy to use and sufficiently accurate to evaluate motor performance. This study aims to develop a 3D markerless motion capture technique, using OpenPose with multiple synchronized video cameras, and examine its accuracy in comparison with optical marker-based motion capture. Participants performed three motor tasks (walking, countermovement jumping, and ball throwing), and these movements measured using both marker-based optical motion capture and OpenPose-based markerless motion capture. The differences in corresponding joint positions, estimated from the two different methods throughout the analysis, were presented as a mean absolute error (MAE). The results demonstrated that, qualitatively, 3D pose estimation using markerless motion capture could correctly reproduce the movements of participants. Quantitatively, of all the mean absolute errors calculated, approximately 47% were <20 mm, and 80% were <30 mm. However, 10% were >40 mm. The primary reason for mean absolute errors exceeding 40 mm was that OpenPose failed to track the participant's pose in 2D images owing to failures, such as recognition of an object as a human body segment or replacing one segment with another depending on the image of each frame. In conclusion, this study demonstrates that, if an algorithm that corrects all apparently wrong tracking can be incorporated into the system, OpenPose-based markerless motion capture can be used for human movement science with an accuracy of 30 mm or less.

8.
Eur J Sport Sci ; 20(5): 606-613, 2020 Jun.
Article in English | MEDLINE | ID: mdl-31335296

ABSTRACT

Abstract This study aims to examine if upper torso rotation is caused mainly by pelvis rotation during baseball pitching from the viewpoint of energetics. Twelve right-handed males participated in this study. Five were and seven had been collegiate baseball pitchers, and all used an overarm style. They threw a baseball as fast and precisely as possible, and data from three strikes were used. A motion capture system consisting of 13 cameras and two force platforms was used to collect the data and calculate joint torques of the thoracic and the lumbar joint. The joint torque of the thoracic and the lumbar joint were calculated using a top-down and a bottom-up approach, respectively. Then, the mechanical energy generation and transfer by the torsional torques were quantified. The mechanical energy generation exerted by the torsional torques of the thoracic and lumbar joints were 0.03 ± 0.03 and 0.15 ± 0.04 J kg-1 m-1, respectively. The mechanical energy transfer exerted by the torsional torques of the thoracic and lumbar joints were 0.72 ± 0.19 and 0.88 ± 0.24 J kg-1 m-1, respectively. These results indicated that torsional torques transferred a substantial amount of mechanical energy from the pelvis to the upper torso. Furthermore, the findings indicate that the mechanical energy transfer exerted by the torsional torques was a major contributor to the upper torso rotation.


Subject(s)
Baseball/physiology , Pelvis/physiology , Torso/physiology , Biomechanical Phenomena , Humans , Male , Rotation , Torque , Young Adult
9.
Am J Physiol Gastrointest Liver Physiol ; 290(5): G1041-50, 2006 May.
Article in English | MEDLINE | ID: mdl-16384872

ABSTRACT

Endothelin (ET)-1 is a potent inducer of peptic ulcers. The roles of ET-1 in ulcer healing, however, have remained unclear, and these were investigated in mice. Gastric ulcers were induced in mice by serosal application of acetic acid. Three days later, mice were given a neutralizing ET-1 antibody or nonimmunized serum. The ulcer size, amount of fibrosis and myofibroblasts, and localization of ET-1 and ET(A/B) receptors were analyzed. To elucidate the mechanisms underlying the effects of ET-1, we examined the proliferation, migration, and release of growth and angiogenic factors in gastric myofibroblasts with or without ET-1. The expression of prepro-ET-1 (an ET-1 precursor) and ET-converting enzyme-1 was examined in gastric myofibroblasts using RT-PCR. Immunoneutralization of ET-1 delayed gastric ulcer healing. The areas of fibrosis and myofibroblasts were smaller in the anti-ET-1 antibody group than in the control. ET-1 was expressed in the gastric epithelium, myofibroblasts, and other cell types. ET(A) receptors, but not ET(B) receptors, were present in myofibroblasts. ET-1 increased proliferation and migration of gastric myofibroblasts. ET-1 stimulated the release of hepatocyte growth factor, VEGF, PGE(2), and IL-6 from gastric myofibroblasts. mRNA for prepro-ET-1 and ET-converting enzyme-1 was also expressed. ET-1 promotes the accumulation of gastric myofibroblasts and collagen fibrils at gastric ulcers. ET-1 also stimulates migration and proliferation of gastric myofibroblasts and enhances the release of growth factors, angiogenic factors, and PGE(2). Thus ET-1 has important roles not only in ulcer formation but also in ulcer healing via mobilizing myofibroblasts and inducing production of stroma-derived factors.


Subject(s)
Endothelin-1/metabolism , Fibroblasts/metabolism , Gastric Mucosa/metabolism , Stomach Ulcer/therapy , Ulcer/metabolism , Angiogenesis Inducing Agents/metabolism , Animals , Antibodies/immunology , Cell Movement , Cell Proliferation , Cytokines/metabolism , Dose-Response Relationship, Drug , Endothelin-1/immunology , Fibroblasts/physiology , Growth Substances/metabolism , Immunohistochemistry , Male , Mice , Mice, Inbred BALB C , Peptides, Cyclic/pharmacology , Placebos , Receptor, Endothelin A/metabolism , Receptor, Endothelin B/metabolism , Stomach/pathology , Time Factors
10.
Cancer Res ; 63(20): 6726-34, 2003 Oct 15.
Article in English | MEDLINE | ID: mdl-14583467

ABSTRACT

Prostaglandin (PG) E(2), a cyclooxygenase (COX) product, and angiotensin II are endogenous and have physiological roles in the body. On the other hand, an inducible isoform of COX (COX-2), insulin-like growth factor (IGF) II, and IGF-I receptor (IGF-IR) are up-regulated in colon carcinoma and might have crucial roles in tumor growth and invasion. The aim of the present study was to investigate the effects of COX-2 inhibitor and drugs blocking the biological activities of angiotensin II [angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs)] on IGF-IR expression and tumor growth in vivo. We also investigated the effects of PGE(2), a major COX-2 product, in cancer cells and the effects of angiotensin II on IGF-IR expression and the underlying mechanism of action. In in vivo studies, tumor growth and IGF-IR expression were investigated in Colon 26 cells inoculated into BALB/c mice. In in vitro studies, the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on IGF-IR expression were analyzed in three colon cancer cell lines (Colon 26, HCA-7, and LS174T). IGF-II-induced cell growth and invasion were analyzed in Colon 26 cells in the presence and absence of NSAIDs (indomethacin and celecoxib) and angiotensin II. Celecoxib at the lowest effective dose for suppression of PG production (3 mg/kg) or an ACE inhibitor/ARB alone did not have a significant effect as compared with controls, although a high dose of celecoxib (>20 mg/kg) suppressed tumor growth. On the other hand, combination therapy with these two categories of drugs significantly reduced tumor growth in vivo. Treatment with both celecoxib and an ACE inhibitor/ARB decreased IGF-IR expression levels in inoculated tumor cells. In in vitro studies, NSAIDs reduced IGF-IR expression in a dose-dependent manner in all three cell lines. NSAIDs also inhibited IGF-II-stimulated growth and invasion in a dose-dependent manner. PGE(2) or angiotensin II treatment reversed the NSAID-induced down-regulation of IGF-IR expression, growth, and invasion. PGE(2) and angiotensin II induced Akt phosphorylation, and LY294002 or wortmannin inhibited PGE(2)- or angiotensin II-induced IGF-IR expression, indicating that PGE(2) and angiotensin II both regulate IGF-IR expression by the same Akt/phosphatidylinositol-3 pathway. Thus, combination therapy with NSAIDs and ACE inhibitors targeting IGF-IR might be a novel and potentially promising strategy for the chemoprevention of colon cancer.


Subject(s)
Angiotensin II/antagonists & inhibitors , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Colonic Neoplasms/drug therapy , Cyclooxygenase Inhibitors/pharmacology , Dinoprostone/physiology , Isoenzymes/antagonists & inhibitors , Protein Serine-Threonine Kinases , Receptor, IGF Type 1/biosynthesis , Angiotensin II/pharmacology , Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Celecoxib , Cell Division/drug effects , Cell Division/physiology , Colonic Neoplasms/metabolism , Colonic Neoplasms/pathology , Cyclooxygenase 1 , Cyclooxygenase 2 , Cyclooxygenase 2 Inhibitors , Cyclooxygenase Inhibitors/administration & dosage , Dinoprostone/antagonists & inhibitors , Drug Synergism , Enalapril/administration & dosage , Enalapril/pharmacology , Humans , Indomethacin/administration & dosage , Indomethacin/pharmacology , Isoenzymes/biosynthesis , Male , Membrane Proteins , Mice , Prostaglandin-Endoperoxide Synthases/biosynthesis , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins c-akt , Pyrazoles , Sulfonamides/administration & dosage , Sulfonamides/pharmacology
11.
J Pharmacol Exp Ther ; 303(3): 1301-8, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12438555

ABSTRACT

Proton pump inhibitors (PPIs) are antiulcer agents that have both gastric antisecretory and mucosal protective actions. The mechanisms of PPI-induced gastric mucosal protection are not known. The present study was designed to examine the mechanism for lansoprazole-induced gastric mucosal protection in rats. Rats were given 0.5, 5, and 50 mg/kg/day lansoprazole alone or both lansoprazole (50 mg/kg/day) and a specific gastrin receptor antagonist 3R-1-(2,2-diethoxyethyl)-((4-methylphenyl)amino-carbonyl methyl)-3-((4-methylphenyl)ureidoindoline-2- one) (AG-041R) (3, 10, and 30 mg/kg/day) for 14 days. Serum gastrin concentrations were measured. The expression of cyclooxygenases (COX-1 and COX-2) in the gastric mucosa was analyzed using Western blotting and immunohistochemical staining. Another series of rats was used to examine the 1) levels of prostaglandin (PG) E2 in gastric mucosa, 2) influences of the drugs on gastric damage caused by absolute ethanol, and 3) effects of a COX-2-specific inhibitor on PGE2 in the gastric mucosa and the mucosal protection afforded by lansoprazole. Lansoprazole dose dependently increased the serum gastrin concentration and enhanced the mucosal expression of COX-2 but not that of COX-1. Lansoprazole increased gastric mucosal PGE2 and reduced gastric damage caused by ethanol. Concomitant administration of AG-041R abolished the lansoprazole-induced COX-2 expression, and increased mucosal PGE2 and mucosal protection. A specific COX-2 inhibitor blocked the lansoprazole-induced increase in mucosal PGE2 and mucosal protection. Activation of gastrin receptors by endogenous gastrin has a pivotal role in the effects of lansoprazole on COX-2 up-regulation and mucosal protection in the rat stomach.


Subject(s)
Gastric Mucosa/drug effects , Isoenzymes/biosynthesis , Omeprazole/analogs & derivatives , Omeprazole/pharmacology , Omeprazole/therapeutic use , Prostaglandin-Endoperoxide Synthases/biosynthesis , Receptors, Cholecystokinin/physiology , Up-Regulation/drug effects , 2-Pyridinylmethylsulfinylbenzimidazoles , Animals , Cyclooxygenase 2 , Cyclooxygenase 2 Inhibitors , Cyclooxygenase Inhibitors/pharmacology , Dinoprostone/biosynthesis , Ethanol/pharmacology , Gastric Mucosa/chemistry , Gastric Mucosa/enzymology , Isoenzymes/analysis , Lansoprazole , Male , Prostaglandin-Endoperoxide Synthases/analysis , Rats , Rats, Sprague-Dawley , Stomach Ulcer/chemically induced , Stomach Ulcer/drug therapy , Stomach Ulcer/enzymology , Up-Regulation/physiology
12.
Am J Physiol Gastrointest Liver Physiol ; 283(6): G1368-78, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12388195

ABSTRACT

Gastrin, PGs, and growth factors have important roles in maintaining gastrointestinal mucosal integrity. Cyclooxygenases (COX-1 and COX-2) are the key enzymes involved in PG synthesis. This study aimed to clarify the mechanisms of gastric mucosal protection by gastrin. Fasted rats were administered subcutaneous gastrin 17 with or without gastrin receptor antagonist YM022 pretreatment. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) and COX-2 expression were examined using Western blot analysis. Another series of experiments investigated 1) PGE(2) levels in gastric mucosa, 2) the protective action of gastrin against gastric damage by acidified ethanol, 3) the effects of a specific HB-EGF-neutralizing antibody on gastrin-induced COX-2 expression, and 4) the effects of a specific COX-2 inhibitor NS-398 on PGE(2) synthesis and the mucosal protection afforded by gastrin. Gastrin dose-dependently increased HB-EGF, COX-2 expression, and PGE(2) levels and reduced gastric damage. However, pretreatment with YM022 dose-dependently abolished such effects of gastrin. A specific HB-EGF- neutralizing antibody and an EGF receptor inhibitor decreased gastrin-induced COX-2 expression. NS-398 blocked gastrin-induced PGE(2) synthesis and mucosal protection. In conclusion, this study demonstrates that gastrin enhances gastric mucosal integrity through COX-2, which is partially mediated by HB-EGF, and PGE(2) upregulation in rats.


Subject(s)
Gastric Mucosa/physiology , Gastrins/pharmacology , Isoenzymes/analysis , Prostaglandin-Endoperoxide Synthases/analysis , Animals , Antibodies/pharmacology , Blotting, Western , Cyclooxygenase 1 , Cyclooxygenase 2 , Cyclooxygenase 2 Inhibitors , Cyclooxygenase Inhibitors/pharmacology , Dinoprostone/analysis , Epidermal Growth Factor/analysis , Epidermal Growth Factor/immunology , Ethanol/pharmacology , Gastric Mucosa/chemistry , Gastric Mucosa/drug effects , Gastric Mucosa/pathology , Gastrins/blood , Heparin-binding EGF-like Growth Factor , Hepatocyte Growth Factor/analysis , Hydrogen-Ion Concentration , Immunoenzyme Techniques , Immunohistochemistry , Intercellular Signaling Peptides and Proteins , Isoenzymes/metabolism , Male , Membrane Proteins , Nitrobenzenes/pharmacology , Prostaglandin-Endoperoxide Synthases/metabolism , Rats , Rats, Sprague-Dawley , Stomach Ulcer/pathology , Sulfonamides/pharmacology
13.
J Gastroenterol Hepatol ; 17(9): 960-5, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12167116

ABSTRACT

BACKGROUND AND AIMS: Helicobacter pylori infection is associated with peptic ulcers; however, it is unclear whether the bacterium delays ulcer healing. We investigated the influence of H. pylori on ulcer healing in mice. We also examined the influence of H. pylori infection on angiogenesis. METHODS: An acetic acid ulcer was made in male BALB/c mice. Three days later (day 0), the animals were inoculated with H. pylori SS1 strain. The healing process of the ulcer was examined macroscopically and microscopically on days 0, 6 and 9. The index of angiogenesis was also determined using carmine dye injection. RESULTS: On day 0, angiogenesis began at the ulcer margin while the mucosal epithelia had not yet regenerated. On days 6 and 9, angiogenesis and epithelial regeneration developed and ulcer size reduced. These phenomena were significantly suppressed in mice infected with H. pylori. CONCLUSION: Helicobacter pylori infection significantly suppressed angiogenesis and delayed ulcer healing. These results indicate that H. pylori plays an important role in ulcer healing.


Subject(s)
Gastric Mucosa/blood supply , Helicobacter Infections/physiopathology , Helicobacter pylori/physiology , Neovascularization, Physiologic , Peptic Ulcer/physiopathology , Wound Healing/physiology , Acetic Acid/toxicity , Animals , Helicobacter Infections/microbiology , Indicators and Reagents/toxicity , Male , Mice , Mice, Inbred BALB C , Models, Animal , Peptic Ulcer/chemically induced , Peptic Ulcer/microbiology
14.
Cancer Res ; 62(5): 1567-72, 2002 Mar 01.
Article in English | MEDLINE | ID: mdl-11888937

ABSTRACT

Cyclooxygenase-2 (COX-2) was recently reported (M. Tsujii and R. N. DuBois, Cell, 83: 493-501, 1995) to affect the metastatic potential of cells. Previous studies (M. Fukuda, Cancer Res., 56: 2237-2244, 1996) indicated that sialyl Lewis antigen expression is correlated with hematogenous metastasis of colon cancer. In the present study, we investigated the interaction between COX-2 activity, expression of sialyl Lewis antigens, in vitro cancer cell adhesion to endothelial cells, and in vivo metastatic potential. Effects of COX-2 activity and prostaglandin E(2) on cell adhesion, expression of sialyl Lewis antigens, and glycosyltransferase genes were determined in Caco-2-m (COX-2 low level), Caco-2-COX-2 (programmed to overexpress COX-2), and HT-29 (COX-2 high level) cells. Metastatic spread of these cells to the liver was also investigated. Caco-2-COX-2 cells had increased SPan-1 levels and increased adherence to endothelial cells via SPan-1 compared with Caco-2-m cells. HT-29 cells expressed sialyl Lewis a and adhered to endothelial cells via sialyl Lewis a. Treatment with a COX-2 inhibitor, celecoxib, decreased SPan-1 and sialyl Lewis a expression and adherence to endothelial cells. beta 3Gal-T5 and ST3Gal III and IV expression was inhibited by celecoxib and was enhanced by prostaglandin E(2) treatment. Caco-2-COX-2 and HT-29 cells metastasized to the liver, whereas Caco-2-m cells did not. Pretreatment with celecoxib reduced the metastatic potential as well as anti-sialyl Lewis antibodies. Our results indicate a direct link between COX-2 and enhanced adhesion of carcinoma cells to endothelial cells, and enhanced liver metastatic potential via accelerated production of sialyl Lewis antigens. COX-2 inhibitors may suppress metastasis.


Subject(s)
Colonic Neoplasms/enzymology , Isoenzymes/physiology , Liver Neoplasms/secondary , Oligosaccharides/analysis , Prostaglandin-Endoperoxide Synthases/physiology , Animals , Caco-2 Cells , Cell Adhesion , Colonic Neoplasms/immunology , Colonic Neoplasms/pathology , Cyclooxygenase 2 , Dinoprostone/biosynthesis , Dinoprostone/pharmacology , Endothelium, Vascular/cytology , Glycosyltransferases/physiology , HT29 Cells , Humans , Male , Membrane Proteins , Mice , Mice, Inbred BALB C , Sialyl Lewis X Antigen
15.
Gastroenterology ; 122(2): 331-9, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11832448

ABSTRACT

BACKGROUND & AIMS: Src activation is correlated with progression of colorectal cancer (CRC). CRCs accompanied by ulcerative colitis, chronic inflammation in the colon, often have elevated Src activity, and ulcerative colitis-related CRCs are more likely to become invasive, whereas Ras activation is rarely associated with this disease. The aim of this study was to investigate the effects of a proinflammatory cytokine, tumor necrosis factor alpha (TNF-alpha), on the invasive properties of epithelial cells constitutively expressing activated Ras or Src. METHODS: A cell line derived from intestinal epithelia was transfected with a v-src- or v-H-ras-expressing vector. The effect of TNF-alpha on morphologic changes in colonies cultured in soft agar was determined. Src protein kinase activity, peroxide production, E-cadherin expression levels, and the phosphorylation status of beta-catenin and E-cadherin were determined. The invasive potential of these cells was determined by measuring cell motility and using an in vitro invasion assay. RESULTS: TNF-alpha altered the colony morphology of src-, but not ras-expressing cells. TNF-alpha increased peroxide production, leading to Src protein expression as well as Src activity in src transfectants. Activation of Src by TNF-alpha led to reduced E-cadherin levels and enhanced invasion of src transfectants. Pyrrolidine dithiocarbamate and herbimycin A inhibited these effects. CONCLUSION: These results indicate that Src kinase activation enhances the response of epithelial cells to TNF-alpha leading to increased invasion through mechanisms that involve production of reactive oxygen intermediates.


Subject(s)
Antineoplastic Agents/pharmacology , Cell Movement/physiology , Oncogene Protein pp60(v-src)/metabolism , Trans-Activators , Tumor Necrosis Factor-alpha/pharmacology , Agar , Animals , Antioxidants/pharmacology , Cadherins/metabolism , Cell Line, Transformed , Cytoskeletal Proteins/metabolism , Hydrogen Peroxide/metabolism , Intestinal Mucosa/cytology , Neoplasm Invasiveness/physiopathology , Oncogene Protein p21(ras)/genetics , Oncogene Protein p21(ras)/metabolism , Oncogene Protein pp60(v-src)/genetics , Oxidative Stress/drug effects , Oxidative Stress/physiology , Phosphotyrosine/metabolism , Pyrrolidines/pharmacology , Rats , Thiocarbamates/pharmacology , Transfection , Tyrosine/metabolism , beta Catenin
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