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Objective To explore the prognostic value and immune infiltration landscape of anoikis-related long noncoding RNAs (arlncRNAs) in lung adenocarcinoma. Methods RNA-seq and clinical data of lung adenocarcinoma were downloaded from the TCGA database, and anoikis-related genes were obtained from the GeneCards and Harmonizome databases. Coexpression, differential, and WGCNA analyses were performed to screen differentially expressed arlncRNAs closely related to the occurrence of lung adenocarcinoma. A prognostic risk model was then constructed based on the arlncRNAs, and its predictive efficacy was further validated. Finally, consensus clustering was used to identify the molecular subtypes associated with anoikis in lung adenocarcinoma. Results Seven prognostic arlncRNAs were identified, and the prognostic risk models established based on them had AUC values of ROC curves greater than 0.7. Survival and immune infiltration analyses revealed that low-risk patients had high overall survival and immune infiltration, implying that they experienced good immune treatment effects. Drug sensitivity analysis showed that the high-risk patients were more sensitive to commonly used chemotherapeutic agents than the low-risk patients. According to the expression of model genes, subtypes C1 and C2 were identified through consensus clustering, and C1 showed a good prognosis. Conclusion The prognostic risk model based on the seven arlncRNAs can effectively predict the prognosis of lung adenocarcinoma patients. The results of immune-related and drug sensitivity analyses provide a reference for the precise individualized treatment of patients with lung adenocarcinoma.
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Anoikis is a type of apoptosis that occurs in response to the loss of adhesion to the extracellular matrix (ECM). Anoikis resistance is a critical mechanism in cancer and contributes to tumor metastasis. Nitric oxide (NO) is frequently upregulated in the tumor area and is considered an important player in cancer metastasis. The aim of this study was to evaluate the effect of NO on adhesiveness, invasiveness, and migration of anoikis-resistant endothelial cells. Here, we report that anoikis-resistant endothelial cells overexpress endothelial nitric oxide synthase. The inhibition of NO release in anoikis-resistant endothelial cells was able to decrease adhesiveness to fibronectin, laminin, and collagen IV. This was accompanied by an increase in cell invasiveness and migration. Furthermore, anoikis-resistant cell lines displayed a decrease in fibronectin and collagen IV protein expression after L-NAME treatment. These alterations in adhesiveness and invasiveness were the consequence of MMP-2 up-regulation observed after NO release inhibition. The decrease in NO levels was able to down-regulate the activating transcription factor 3 (ATF3) protein expression. ATF3 represses MMP-2 gene expression by antagonizing p53-dependent trans-activation of the MMP-2 promoter. We speculate that the increased release of NO by anoikis-resistant endothelial cells acted as a response to restrict the MMP-2 action, interfering in MMP-2 gene expression via ATF3 regulation. The up-regulation of nitric oxide by anoikis-resistant endothelial cells is an important response to restrict tumorigenic behavior. Without this mechanism, invasiveness and migration potential would be even higher, as shown after L-NAME treatment.
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Epithelial ovarian cancer (EOC) is one of the leading causes of death from gynecologic cancers and peritoneal dissemination is the major cause of death in patients with EOC. Although the loss of 4.1N is associated with increased risk of malignancy, its association with EOC remains unclear. To explore the underlying mechanism of the loss of 4.1N in constitutive activation of epithelial-mesenchymal transition (EMT) and matrix-detached cell death resistance, we investigated samples from 268 formalin-fixed EOC tissues and performed various in vitro and in vivo assays. We report that the loss of 4.1N correlated with progress in clinical stage, as well as poor survival in EOC patients. The loss of 4.1N induces EMT in adherent EOC cells and its expression inhibits anoikis resistance and EMT by directly binding and accelerating the degradation of 14-3-3 in suspension EOC cells. Furthermore, the loss of 4.1N could increase the rate of entosis, which aggravates cell death resistance in suspension EOC cells. Moreover, xenograft tumors in nude mice also show that the loss of 4.1N can aggravate peritoneal dissemination of EOC cells. Single-agent and combination therapy with a ROCK inhibitor and a 14-3-3 antagonist can reduce tumor spread to varying degrees. Our results not only define the vital role of 4.1N loss in inducing EMT, anoikis resistance, and entosis-induced cell death resistance in EOC, but also suggest that individual or combined application of 4.1N, 14-3-3 antagonists, and entosis inhibitors may be a promising therapeutic approach for the treatment of EOC.
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Objective:To investigate the effect of modified Si Junzitang on the expression of fibrous protein-5（Fibulin-5）， phosphorylated protein kinase B（p-Akt ）in hippocampus of rats after cerebral ischemia-reperfusion （I/R） injury and the anoikis of nerve cells. Method:The 60 male SD rats of SPF grade were randomly divided into sham operation group， model group， Edaravone group （3.2 mg·kg-1）and modified Si Junzitang high， medium and low-dose groups（19.08，9.54，4.77 g·kg-1）.The middle cerebral artery occlusion （MCAO） model was established by suture method，the rats were killed 7 days later，neurological deficit score was evaluated before the death，histopathological observation was performed by hematoxylin eosin staining， apoptosis index of nerve cells was detected by TdT-mediated dUTP nick end labeling（TUNEL）staining， the expression of Fibulin-5， p-Akt and protein in ischemic hippocampus were detected by immunohistochemistry and Western blot. Result:The neurological deficit score showed that，compared with the sham operation group， the neurological deficit score of the model group was significantly increased （P<0.01）， compared with model group， the neurological deficit score of Edaravone group，the high， medium， low dose groups of modified Si Junzitang were decreased （P<0.05，P<0.01）. Immunohistochemical results showed that，compared with the sham operation group， the expression of Fibulin-5， p-Akt protein and the apoptosis index of nerve cells in the model group were significantly increased （P<0.05，P<0.01）， compared with model group， the protein expressions of Fibulin-5 and p-Akt in Edaravone group， high， medium and low-dose groups of modified Si Junzitang were significantly increased （P<0.05，P<0.01）， and the apoptosis index of nerve cells was obvious，there was a significant decrease （P<0.05，P<0.01）. Western blot results showed that，compared with the sham operation group， the relative expression of Fibulin-5 and p-Akt protein in the model group was significantly down-regulated （P<0.01）， compared with model group， the protein expressions of Fibulin-5 and p-Akt in the Edaravone group， the high， medium and low-dose groups of modified Si Junzitang were significantly up-regulated （P<0.05，P<0.01）. Conclusion:The modified Si Junzitang may stabilize the extracellular matrix （ECM） Fibulin-5， increase the adhesion of ECM to cells and promote the expression of p-Akt protein， thus inhibiting neuronal apoptosis and protecting cerebral ischemia injury.
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Objective: To determine the expression of anoikis factor Bcl2 inhibitor of transcription 1 (Bit1), epithelial-mesenchymal transformation (EMT) marker E-cadherin and P16INK4a in tumor budding and central tumor of cervical squamous cell carcinoma, and to explore the significance of Bit1 and E-cadherin expression in the process of obtaining high invasiveness of cervical cancer and their relationship with P16INK4a expression. Methods: A total of 77 paraffin-embedded specimens of cervical squamous cell carcinoma were collected from the Department of Pathology of Gansu Provincial Cancer Hospital between 2014 and 2018. The expression levels of Bit1, E-cadherin and P16INK4a in tumor budding and central tumor of these specimens were detected by immunohistochemistry. Taking the median scores of protein expression in the central tumor and tumor budding as dividing points, the specimens were divided into high expression group and low expression group. The differences of Bit1 and E-cadherin expression under different p16INK4a expression and their relationship with the clinicopathological characteristics of the patients were analyzed. The correlation between Bit1 and E-cadherin expression in central tumor and tumor budding was explored. The χ2 test, continuous correction χ2 test and Spearman rank correlation analysis were used for statistical analysis. Results: In 77 cases of paraffin-embedded specimens of cervical squamous cell carcinoma, the high expression rates of P16INK4a, E-cadherin and Bit1 in central tumor and tumor budding were 32.5% (25/77), 67.5% (52/77) and 63.6% (49/77), and 67.5% (52/77), 33.8% (26/77) and 37.7% (29/77), respectively, and the differences were significant (χ2 18.935, 17.561 and 10.391, all P < 0.01). Both in central tumor and in tumor budding, there were no significant differences in Bit1 or E-cadherin expression between high and low P16INK4a expression regions (all P < 0.05). In central tumor, the low expression of Bit-1 was related to lymphovascular invasion and lymph node metastasis (χ2 5.053 and 4.400, both P < 0.05). In tumor budding, the low expression levels of E-cadherin and Bit-1 were both associated with lymph node metastasis (χ2 5.580 and 7.573, both P < 0.05). Spearman rank correlation analysis showed that there was positive correlation between E-cadherin and Bit1 expression in central tumor and tumor budding (r 0.287, P = 0.011; r 0.236, P < 0.039). Conclusion: The increased invasiveness of cervical cancer may be related to the decreased expression of Bit1 and E-cadherin and the increased expression of P16INK4a. Cervical cancer cells may acquire high invasiveness by inhibiting Bit1 to obtain anoikis resistance and affecting the EMT, but P16INK4a is not involved in this process.
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Objective@#Modern medical research has proven that human diseases are directly or indirectly related to genes. At the same time, genetic research has also brought updates to diagnostic techniques. Olfactomedin-like 3 (OLFML3) gene is a novel and clinically valuable gene. In order to better understand the role of OLFML3 in human diseases, we discuss and analyze the characteristics, function, and regulation mechanism of the OLFML3 gene in this review.@*Data sources@#A comprehensive search in PubMed and ScienceDirect database for English up to March 2019, with the keywords of "Olfactomedin-like 3," "Olfactomedin," "extracellular matrix," "Transforming Growth Factor β1," "anoikis-resistance," and "microRNA-155."@*Study selection@#Careful review of all relevant literature, the references of the retrieved articles were also screened to search for potentially relevant papers.@*Results@#OLFML3 is a secreted glycoprotein with 406 amino acid residues, belonging to the Olfactomedin (OLF) family. Due to the particularity of its structure and differential expression, OLFML3 has unique biological functions that could be distinct from other members in the OLF family. The currently known functions include embryonic development function and tumorigenesis. The regulation mechanism is still under investigation. It is directly related to many human diseases.@*Conclusions@#OLFML3 is a multifunctional glycoprotein that is closely involved in embryonic development, tumor invasion, and metastasis. Unfortunately, current research on this important molecule is still very limited. Further investigations on the possible mechanism of OLFML3 biological functions and modulation will help us develop better diagnostics and treatments.
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The anoikis resistance confers the ability of cancer cells to survive and metastasize in the blood circulation without adhesion,but its effect and mechanism in intrahepatic and distant metastasis of hepatocellular carcinoma has not been fully elucidated.Recent studies have shown that certain factors or drugs may inhibit anoikis of hepatoma cells through some signaling pathways.These signaling pathways are not completely separated,they are interconnected to promote metastasis of hepatocellular carcinoma.Liver is the metabolic center of many substances,and many related factors can promote metastasis of hepatocellular carcinoma through inhibiting anoikis.In this review,we summarized the signaling pathways of anoikis resistance of hepatocellular carcinoma.
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Anoikis is a form of apoptosis induced upon cell detachment from extracellular matrix.It has been determined that acquisition of resistance to anoikis is a critical step for tumor cell metastasis.MiR-21,the most prominent oncomiR,plays an important role in tumor progression.In this study,we revealed that up-regulation of miR-21 in human esophageal adenocarcinoma (EA) is associated with lymph node metastasis and poor survival rate.Because of the established anti-apoptosis effect of miR-21,it is tempting to speculate that miR-21 might contribute to tumor metastasis by regulating anoikis,qRT-PCR analysis demonstrated that miR-21 expression in OE33/AR cells (subpopulation of human EA OE33 cells that acquired resistance to anoikis) was significantly increased.Also,transfection of miR-21 mimics provided OE33 cells resisting to anoikis.By luciferase assays,we verified that PDCD4 and PTEN were the functional targets of miR-21.In mouse model,via tail vein injection experiment,we showed that the metastasis formation of OE33 cells in vivo could be mediated by changing the miR-21 expression pattern.Taken together,our findings suggested that miR-21 was involved in the regulation of anoikis in human EA cells.Targeting miR-21 may provide a novel strategy to prevent metastasis.
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Anoikis is a form of apoptosis induced upon cell detachment from extracellular matrix.It has been determined that acquisition of resistance to anoikis is a critical step for tumor cell metastasis.MiR-21,the most prominent oncomiR,plays an important role in tumor progression.In this study,we revealed that up-regulation of miR-21 in human esophageal adenocarcinoma (EA) is associated with lymph node metastasis and poor survival rate.Because of the established anti-apoptosis effect of miR-21,it is tempting to speculate that miR-21 might contribute to tumor metastasis by regulating anoikis,qRT-PCR analysis demonstrated that miR-21 expression in OE33/AR cells (subpopulation of human EA OE33 cells that acquired resistance to anoikis) was significantly increased.Also,transfection of miR-21 mimics provided OE33 cells resisting to anoikis.By luciferase assays,we verified that PDCD4 and PTEN were the functional targets of miR-21.In mouse model,via tail vein injection experiment,we showed that the metastasis formation of OE33 cells in vivo could be mediated by changing the miR-21 expression pattern.Taken together,our findings suggested that miR-21 was involved in the regulation of anoikis in human EA cells.Targeting miR-21 may provide a novel strategy to prevent metastasis.
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Objective@#To investigate the potential role of Bit1 in the pathogenesis of pancreatic ductal cancer cells(PDAC) and its potential clinical application value.@*Methods@#Real-time PCR and Western blot were employed to detect the expression of Bit1 in six pancreatic cancer cells, then the tool cells were selected to further study the function of Bit1.PolyHEMA was used to monitor the suspended cell culture condition in vitro.The invasion and migration abilities of pancreatic cancer cells were detected through Transwell assay. Western blot and confocal assay were used to explore the potential mechanism of Bit1 in the process of metastasis.The expression of Bit1 was detected through tissue microarray, the potential relationship between Bit1 and other clinical factors were analyzed.@*Results@#The results of real-time PCR and Western blot indicated that the expression of Bit1 was highest in the PANC1 cells and lowest in the Mia paca2 cells (gene: 3.13±0.40 vs. 1.00±0.35, protein: 1.77±1.00 vs. 0.23±0.45). The shBit1 PANC1 and Bit1-OE(over expression) Mia paca2 cells were successfully constructed.Bit1 over expression could promote the anoikis rate of Mia paca2 cells, and Bit knockdown could inhibit the anoikis incidence.Bit1 over expression suppressed the motility and invasion of Mia paca2 cells, but Bit1 knockdown could accelerate the migration and invasion ability of PANC1 cells.Bit1 could potentially affect pancreatic cancer cells′ malignant behaviors through epithelial-mesenchymal transition process.Bit1 expression was significantly associated with pancreatic cancer′s neural invasion (P<0.05).@*Conclusions@#Bit1 could affect the anoikis incidence of pancreatic cancer, Bit1 negatively affect the migration and invasion abilities of PDAC, the EMT process was potentially involved in the whole modulation process.Bit1 expression is associated with neural invasion in pancreatic cancer patients.
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Objective To investigate the effects of estrogen ( E2) on the resistance to anoikis and a possible role of extracellular signal-regulated kinse ( ERK)-focal adhesion kinse ( FAK) signaling in the effect of estrogen to under-stand its underlying mechanism .Methods Poly-Hema-coated culture of human breast cancer cell line MCF-7 was used to induce anoikis .Cells were treated with E2 and/or pretreated with MEK or FAK inhibitors .Western blot was used to assess the phosphorylation of ERK and FAK , trypan blue staining and cell counting were employed to evaluate cell viability , and Hoechst staining was used to check apoptosis .Results Suspension culture greatly re-duced cell survival (P<0.01), and exposure of MCF-7 cells to E2 (10 nmol/L) led to a significantly increased resistance to anoikis and survival ( P<0.05 ) as compared to DMSO .Meanwhile , E2 induced increased phospho-rylation of both ERK and FAK .Pharmacological inhibition of MEK with U 0126 ( 10 μmol/L ) reduced E2-in-creased cell survival by 57.48%(P<0.01) and E2-decreased anoikis;Treatment with FAK inhibitor (10μmol/L) attenuated E2-enhanced cell survival by 53.59% ( P<0.01 ) and E2-reduced apoptosis .Conclusions E2 con-tributes to the enhanced cell viability and increased resistance to anoikis in MCF-7 breast cancer cells , and ERK-FAK signaling may be involved in the E 2-stimulated survival during suspension culture of MCF-7 cells.
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Anoikis,a specific form of programmed cell death,is triggered by cell detachment from extracellular matrix or adjacent cell.Studies have found that the most kinds of tumor cells had anoikis resistance characteristic,which may inhibit pro-apoptosis protein,block anoikis inside and outside pathways,up-regulate pro-survival factor signals,and promote survival,invasion and metastasis of tumor cells in the end.The review summarized the mechanism of anoikis and the relationship between anoikis and tumor invasion and the metastasis.
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Objective To investigate the effect of hypoxia micro?environment on anoikis in human high?metastatic cell line 95D of giant cell carci?noma of lung. Methods Suspension technology was used to culture 95D to establish the model of anoikis?resistant 95D cells. Hypoxic culture was conducted in the experimental group,and regular culture was conducted in the control group. The effect of hypoxia on proliferation of anoikis?resis?tant 95D was investigated by MTT and the apoptosis in the two groups were detected by flow cytometer. The invasive ability of the cells was assessed by Transwell test. The effect of hypoxia on the expression of HIF?1α,VEGF and MMP?2 in anoikis?resistant 95D was detected by Western blot. Re?sults The growth rate of the anoikis?resistant 95D cells treated with hypoxia was 52.9%,and the apoptosis rate of these cells was higher than that in the non?hypoxic group(40.4%vs 21.7%,P<0.05). The treatment of hypoxia down?regulated the invasive ability,the number of migration cells un?der hypoxia was higher than that in the control group,with statistical significance(40.1±6.7 vs 12.5±7.9,P<0.05). The up?regulation of HIF?1α, the down?regulation of VEGF and MMP?2 were observed in the group of hypoxia. Conclusion During anoikis of human high?metastatic lung can?cer cell line 95D,hypoxia inhibited the survival ability and the metastasis ability of anoikis?resistant cells,which,however,might be the early mani?festation of hypoxia.
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Pancreatic cancer is a notorious disease with a poor prognosis and low survival rates, which is due to limited advances in understanding of the molecular mechanism and inadequate development of effective treatment options over the decades. In previous studies, we demonstrated that a novel soluble protein named pancreatic adenocarcinoma up-regulated factor (PAUF) acts on tumor and immune cells and plays an important role in metastasis and progression of pancreatic cancer. Here we show that PAUF promotes adhesiveness of pancreatic cancer cells to various extracellular matrix (ECM). Our results further support a positive correlation of activation and expression of focal adhesion kinase (FAK), a key player in tumor cell metastasis and survival, with PAUF expression. PAUF-mediated adhesiveness was significantly attenuated upon blockade of the FAK pathway. Moreover, PAUF appeared to enhance resistance of pancreatic cancer cells to anoikis via modulation of FAK. Our results suggest that PAUF-mediated FAK activation plays an important role in pancreatic cancer progression.
Subject(s)
Humans , Anoikis/genetics , Cell Line, Tumor , Focal Adhesion Protein-Tyrosine Kinases/metabolism , Focal Adhesions/genetics , Lectins/genetics , Pancreatic Neoplasms/enzymology , Proto-Oncogene Proteins pp60(c-src)/metabolism , Signal Transduction/geneticsABSTRACT
La muerte celular programada es un evento fisiológico durante el desarrollo. En el encéfalo y la médula espinal, este proceso determina el número y la localización de los diferentes tipos celulares. En el sistema nervioso del adulto, la muerte celular programada o apoptosis está más restringida, pero puede jugar un papel determinante en enfermedades crónicas o agudas. Al contrario de otros tejidos en los cuales la apoptosis está documentada ampliamente desde el punto de vista morfológico, en el sistema nervioso central la evidencia en este sentido es escasa. A pesar de esto, existe consenso acerca de la activación de diferentes sistemas de señalización apoptótica. En el presente artículo se intenta resumir las principales vías de señalización apoptótica identificadas en el tejido nervioso. Considerando que las vías apoptóticas son múltiples, los tipos neuronales diversos y especializados y que la respuesta neuronal a la lesión y la supervivencia dependen del contexto de la célula en el tejido (preservación de la conectividad, integridad glial y matriz extracelular, flujo sanguíneo y disponibilidad de factores tróficos), lo que es relevante en el proceso apoptótico en un sector del cerebro puede no serlo en otro.
Programmed cell death occurs as a physiological process during development. In the brain and spinal cord this event determines the number and location of the different cell types. In adulthood, programmed cell death or apoptosis is more restricted but it may play a major role in different acute and chronic pathological entities. However, in contrast to other tissues where apoptosis has been widely documented from a morphological point of view, in the central nervous system complete anatomical evidence of apoptosis is scanty. In spite of this there is consensus about the activation of different signal systems associated to programmed cell death. In the present article we attempt to summarize the main apoptotic pathways so far identified in nervous tissue. Considering that apoptotic pathways are multiple, the neuronal cell types are highly diverse and specialized and that neuronal response to injury and survival depends upon tissue context, (i.e., preservation of connectivity, glial integrity and cell matrix, blood supply and trophic factors availability) what is relevant for the apoptotic process in a sector of the brain may not be important in another.
Subject(s)
Caspases , Ischemia , Neurodegenerative Diseases , Proteins , Wounds and InjuriesABSTRACT
Cyclooxygenase-2 (COX-2) has been reported to be associated with tumor development and progression as well as to protect cells from apoptosis induced by various cellular stresses. Through a tetracycline-regulated COX-2 overexpression system, we found that COX-2 inhibits detachment-induced apoptosis (anoikis) in a human bladder cancer cell line, EJ. We also found that the inhibition of anoikis by COX-2 results from activation of the PI-3K/Akt pathway as evidenced by suppression of the COX-2 effect on anoikis by a PI-3K inhibitor, LY294002. Furthermore, COX-2 enhanced Mcl-1 expression in the anoikis process, implying that Mcl-1 also may be involved in mediating the survival function of COX-2. Together, these results suggest that COX-2 inhibits anoikis by activation of the PI-3K/Akt pathway and probably by enhancement of Mcl-1 expression in human bladder cancer cells. This anti- anoikis effect of COX-2 may be a part of mechanisms to promote tumor development and progression.
Subject(s)
Humans , Phosphatidylinositol 3-Kinase/metabolism , Anoikis/physiology , Urinary Bladder Neoplasms/metabolism , Enzyme Activation , Neoplasm Proteins/metabolism , Prostaglandin-Endoperoxide Synthases/metabolism , Protein Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Signal Transduction , Transfection , Tumor Cells, CulturedABSTRACT
Objective To obtain anoikis-resistant cells from human osteosarcoma cell line hFOB1.19 and investigate its biological characteristics.Methods The osteosarcoma cell line we used was malignant transformed immortalized human fetal osteoblastic human cells(hFOB1.19)which was transformed in our lab(called transformant in this paper).We have used anti-adhesion cell culture method to mimic detachment of tumor cells from extracellular matrix(ECM)to obtain anoikis-resistant variants.Transmission electron microscopy and fluorescence microscopy were used to observe the morphological changes,flow cytometry was used to observe the apoptotic rate.The growth characteristic was observed by MTT.The migration characteristics was examined by transwell cell culture system.Results Typical apoptotic cells were seen after de-adhesion culture.The apoptotic rate of the transformant at 24,48 and 72 h showed a gradually increasing tendency.The apoptotic rate of anoikis-resistant cells was lower than that of the transformant at the same time point.Compared with the transformant,the anoikis-resistant variants had stronger ability in proliferation and in migration with statistical significance(P
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Objective To explore the expression of caspase-3 and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors in the CD4+ and CD8+ T cells of systemic lupus erythematosus (SLE)patients. Methods The CD4+ and CD8+T cells from peripheral blood of 20 SLE patients and 10 healthy volunteers were separated using magnetic cell sorting system (MACS), reverse transcription-polymerase chain reaction (RT-PCR) was used to test the expression of caspase-3 and TRAIL receptors in CD4+ and CD8+T cells of SLE patients and healthy volunteers. Results The CD8+T cells from SLE patients had significantly higher caspase-3 (P=0.003) and TRAIL-R2 (P=0.024) expression than those from healthy volunteers. Conclusion The TRAIL-R2 signal pathway may be a possible important pathway to the apoptosis of T cells in SLE patients.
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Background and purpose:TrkB,a neurotrophic tyrosine kinase receptor,serves as a potent and specific suppressor of anoikis of non-malignant epithelial cells,and induces high invasion capacity in these cells.TrkB over-expression has been associated with chemotherapy resistance and poor survival in neuroblastoma and some other highly aggressive cancers.However,the relationship of the expression of TrkB to anoikis resistance in ovarian cancer cells has rarely been reported in literature.This study investigated the expression and significance of anoikis- suppressor TrkB in OVCAR-3 ovarian cancer cells.Methods:The expression of TrkB and its ligand BDNF was evaluated in OVCAR-3 ovarian cancer cells under different culture conditions by RT-PCR and Western blot.Results: TrkB mRNA was overexpressed in multicellular spheroids(cell-spheroids,anchorage-independent culture,AIC)as compared to that in OVCAR-3 cells(adhesive-cells,adhesive culture,AC),(35.3?0.7)% versus(23.5?0.5)%;but BDNF mRNA expression was the opposite to the above situation,(41.4?0.6)% versus(32.24?0.7)%(P
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Anoikis is a special programmed cell death and plays important roles in both physiological regulation and pathogenesis of many diseases, including atherosclerosis, acute coronary syndrome, cardiac failure, aneurysm and tumors. This review focuses on the association of the anoikis with instability and rupture of atherosclerotic plaque.