Korean J Phys Anthropol.  2007 Sep;20(3):225-233.

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

• Kim SM
• Kim JM
• Jeon JS
• Ahn ZS
• Kim DY
• Suh JS
• Park KH
• Park JH
• Kim DJ
• Hahn JH

Abstract

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.

Keyword

CD98; beta1 integrin; Tumor cell invasion; Cell-ECM adhesion; FAK; Actin; Cytoskeleton

MeSH Terms

Actins
Antigens, CD29
Breast Neoplasms*
Breast*
Cell Movement
Collagen
Cytochalasin D
Cytoskeleton
Edetic Acid
Extracellular Matrix
Fibronectins
Focal Adhesion Protein-Tyrosine Kinases
Glycoproteins
Humans*
Immunohistochemistry
Indicators and Reagents
Laminin
Liposomes
MCF-7 Cells*
Phalloidine
Phosphorylation
Phosphotransferases
Actins
Antigens, CD29
Collagen
Cytochalasin D
Edetic Acid
Fibronectins
Focal Adhesion Protein-Tyrosine Kinases
Glycoproteins
Indicators and Reagents
Laminin
Liposomes
Phalloidine
Phosphotransferases