Effect of silencing CD98hc expression on MDA-MB-231 breast cancer cells proliferation and invasion / 临床与实验病理学杂志

Purpose To investigate the effect of silencing of CD98hc on proliferation,migration and invasion of MDA-MB-231 breast cancer cells.Methods RNA interfere technology was used to silence CD98hc in MDA-MB-231 cells.MDA-MB-231 cells (CD98hc-shRNA) with stable low expression of CD98hc and Vector control was obtained.Western blot and qRT-PCR were used to verify the down-regulation of CD98hc.MTT assay was used to test the cell proliferation.Transwell migration and invasion experiment were used to assay cell migration and invasion.Results The expression levels of CD98hc was down-regulated by CD98hc-shRNA in the MDA-MB-231 breast cancer cells.Compared to that of blank cells (0.706 ± 0.013),vector control (0.724 ± 0.018),the cell proliferation potency of CD98hc-shRNA cells (0.580-0.035) was significantly inhibited (P ＜ 0.05),and the cell migration and invasion potency also were inhibited (P ＜ 0.05),there is on significant different between blank cells and vector control (P ＜ 0.05).Conclusion CD98hc might be involved in the regulation of breast cancer cell biological behaviors.

Molecular association of CD98, CD29, and CD147 critically mediates monocytic U937 cell adhesion

Adhesion events of monocytes represent an important step in inflammatory responses induced by chemokines. The β1-integrin CD29 is a major adhesion molecule regulating leukocyte migration and extravasation. Although several adhesion molecules have been known as regulators of CD29, the molecular interactions between CD29 and its regulatory adhesion molecules (such as CD98 and CD147) have not been fully elucidated. Therefore, in this study, we examined whether these molecules are functionally, biochemically, and cell-biologically associated using monocytic U937 cells treated with aggregation-stimulating and blocking antibodies, as well as enzyme inhibitors. The surface levels of CD29, CD98, and CD147 (but not CD43, CD44, and CD82) were increased. The activation of CD29, CD98, and CD147 by ligation of them with aggregation-activating antibodies triggered the induction of cell-cell adhesion, and sensitivity to various enzyme inhibitors and aggregation-blocking antibodies was similar for CD29-, CD98-, and CD147-induced U937 cell aggregation. Molecular association between these molecules and the actin cytoskeleton was confirmed by confocal microscopy and immunoprecipitation. These results strongly suggest that CD29 might be modulated by its biochemical and cellular regulators, including CD98 and CD147, via the actin cytoskeleton.

Initial study on the role of bacterial flagellin and CD98 in ulcerative colitis / 中华消化杂志

Objective To investigate the role of bacterial flagellin and CD98 in ulcerative colitis (UC).Methods A total of 60 first episode patients with active UC were recruited,including 30 mild and 30 moderate to severe UC cases.The serum of 30 healthy volunteers and normal intestinal tissues surgically removed from 15 colon cancer patients (more than 5 cm away from surgical margins) were collected as control.The content of bacterial flagellin antibodies in peripheral blood were measured with enzyme-linked immunosorbent assay (ELISA).The expression of CD98 in peripheral blood T lymphocyte was measured by flow cytometry (FACS).The expression of bacterial flagellin protein in intestinal mucosa and CD98 in intestinal epithelial basement membrane was tested by immunohistochemistry (IHC).The comparison between two groups was performed with the SNK-q method,the R×C table x2 test was used to analyze the counted data,and the Spearman correlation was used to analyze the rank materials.Results The peripheral blood concentration of bacteria flagella protein antibody of control group,mild UC group and moderate to severe group showed an upward trend,which was (7.603±2.118) pg/ml,(13.702±3.131) pg/ml and (20.813±3.004) pg/ml respectively,and the differences among groups were statistically significant (F=13.57,P＜0.01).The expression percentage of bacteria flagella protein in intestinal mucosa of the three groups also showed an upward trend,which was 3/15,56.67％ and 73.33％ respectively,and the differences among groups were statistically significant (x2 =11.553,P=0.003).The positive rate of CD98 expression in peripheral blood T lymphocytes of the three groups showed an upward trend,which was (28.42±4.31)％,(32.45±6.71)％ and (43.40±5.09) ％ respectively,and the differences among groups were statistically significant (x2 =10.110,P=0.007).The positive rate of CD98 expression in intestinal epithelial cells of the three groups also showed an upward trend,which was 1/15,36.67 ％ and 66.67％ respectively,and the differences among groups were statistically significant (x2 =5.400,P＜0.05).There was positive correlation between the peripheral blood concentration of bacteria flagella protein antibody and the expression of CD98 in peripheral blood T lymphocytes (r=0.548,P＜0.05).Conclusion Bacterial flagellin and CD98 may be important factors causing inflammatory reaction activity in UC.

CD98 in lung cancer / 国际肿瘤学杂志

CD98 is a transmembrane heterodimer of cell surface.It regulates cell signaling pathway by activating some correlated proteins,and controls cell polarization,proliferation,adhesion and migration.CD98 plays an important role in the development of cancer and may be a novel tumor marker for diagnosis and prognosis in lung cancer.

Induction of Upregulation and Downregulation of the T-Cell Activation Marker CD98 in Patients Undergoing Contrast-Enhanced CT with Iodinated Non-Ionic Dimeric Contrast Medium

OBJECTIVE: This study was designed to determine prospectively the expression of the multifunctional CD98 protein in peripheral white blood cells in patients receiving iodinated contrast media (CM) for a computed tomography (CT) examination. MATERIALS AND METHODS: In 12 adult patients that received non-ionic dimeric CM (iosimenol or iodixanol), the expression of CD98 was analyzed from samples of peripheral white blood cells obtained prior to, one hour, and 24 hours after CM injection by the use of flow cytometry analysis and the use of the direct immunofluorescence technique. RESULTS: Overall, expression of CD98 was significantly downregulated 24 hours after CM injection (51.9% +/- 10.8% vs. 38.8% +/- 16.9%; p < 0.04). Patients that received iosimenol exhibited a more pronounced but not significant decrease of CD98 expression both one hour and 24 hours after CM injection. In an analysis of specific patient responses, CD98 downregulation occurred in eight patients. In two patients, CD98 was upregulated, and in the remaining two patients, expression remained unchanged. No patient acquired an adverse CM reaction. CONCLUSION: This is the first demonstration that CM may be a regulator of CD98 expression. To determine if upregulation is associated with an increased risk for the acquisition of an adverse CM-induced hypersensitivity reaction and if downregulation is associated without a risk for the acquisition of an adverse CM-induced hypersensitivity reaction, further studies with a larger population of patients are required.

CD98 activation increases surface expression and clusteringof beta 1 integrins in MCF-7 cells through FAK/Src- and cytoskeleton-independent mechanisms

CD98, a disulfide-linked 125-kDa heterodimeric type II transmembrane glycoprotein, regulates beta 1 integrin- mediated cell adhesion. However, the molecular mechanisms underlying CD98-mediated activation of beta 1 integrin are presently unclear. In this study, the effects of CD98 signaling on the expression and clustering of beta 1 integrin were investigated. Activation of CD98 augmented surface expression of beta 1 integrin on MCF-7 cells. Cross-linking CD98 induced clustering of beta 1 integrins. Inhibition of phosphorylation of focal adhesion kimase (FAK) by PP2, an inhibitor of Src family kinase, reduced cell-extracellular matrix adhesion, but not surface expression and clustering of beta1 integrin on MCF-7 cells. This result was confirmed by over-expression of dominant negative forms of FAK. In addition, phalloidin or cytochalasin D inhibited CD98-mediated induction of cell-ECM adhesion, but not surface expression and clustering of b1 integrins. The inhibitory effects of PP2, cytochalasin D or phalloidin on CD98-stimulated cell adhesion were diminished by pretreatment of cells with Mn2+, which is shown to induce conformational change of integrins. These results provide the first evidence that CD98 activation increases not only beta1 integrin affinity but also its surface expression and clustering and the latter is independent of FAK/Src and cytoskeleton.

CD98 Activation Increases the Invasion of Human Breast Carcinoma MCF-7 Cells / 체질인류학회지

CD98, a disulfide-linked 125-kDa heterodimeric type II transmembrane glycoprotein, regulates the func-tions of beta1 integrin, suggesting that it may play a role in tumor cell invasion. In this study, the effects of CD98 signaling on the adhesion and invasion of tumor cells were investigated. The expression of CD98 on MCF-7 human breast carcinoma cells was confirmed by immunohistochemistry. The effects of CD98 activation on the adhesion to extracellular matrix (ECM) and invasion of MCF-7 cells were determined by adhesion assay and cell invasion assay. Dominant negative forms of focal adhesion kinase (FAK) were transiently transfected into MCF-7 cells using liposome reagents. CD98 stimulation increased the adhesion of MCF-7 cells to fibronectin, laminin and collagen IV. Activation of CD98 augmented the invasion rate of MCF-7 cells through ECM. EDTA or a function-blocking anti-beta1 integrin mAb suppressed the effect of CD98 on invasiveness. Inhibition of phosphorylation of FAK by PP2, an inhibitor of Src family kinase, reduced CD98-induced invasion of MCF-7 cells. This result was confirmed by over-expression of dominant negative forms of FAK. In addition, cytochalasin D or phalloidin inhibited CD98-mediated induction of tumor cell invasion. Inhibitory effects of PP2, cytochalasin D or phalloidin on CD98-stimulated invasion of MCF-7 cells were diminished by pretreatment of cells with Mn++, which is shown to induce conformational change of beta1 intgerin. These results provide the first evidence that CD98 activation increases tumor cell invasion by activating beta1 integrin affinity, and that FAK phosphorylation and subsequent cytoskeletal reorganization may be essential for CD98-mediated regulation of cell motility.