Overexpression of tetraspanins affects multiple myeloma cell survival and invasive potential

• Published in: The FASEB journal Vol. 21; no. 3; pp. 691 - 699
• Main Authors: Tohami, Tali, Drucker, Liat, Shapiro, Hava, Radnay, Judith, Lishner, Michael
• Format: Journal Article
• Language: English
• Published: United States The Federation of American Societies for Experimental Biology 01.03.2007
• Subjects: Animals; Cell Cycle - physiology; Cell Proliferation; Cell Survival - physiology; Gene Expression; Humans; Membrane Proteins - genetics; Membrane Proteins - metabolism; Membrane Proteins - physiology; Multiple Myeloma - pathology; Neoplasm Invasiveness; Tetraspanins; Tumor Cells, Cultured
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.06-6610com

Cellular interactions with microenvironmental components are critical in multiple myeloma (MM) and impede effective disease treatment. Membranal-embedded tetraspanins, associated with metastasis suppression, are underexpressed in MM. We aimed to investigate the consequences of CD81/CD82 tetraspanins over-expression in MM cell lines. CAG and RPMI 8226 were transfected with pEGFP-N1/C1 fusion vectors of CD81/CD82. Employing flow cytometry, immunocytochemistry, and activity assays we assessed transfected cells for: morphology, survival, death, caspases, cell cycle, proliferation, oxidative stress, adhesion, motility and invasion. Overexpressed CD81/CD82 pEGFP-N1 vectors reduced survival without elevation of pre-G1 or AnnexinV+/7AAD- and independently of caspases. Decreased Ki67 and elevated intracellular glutathione were detected. No perturbations in cell cycle distribution were observed. The pEGFP-C1 vectors of CD81/CD82 caused reduction of MM cell adherence with/without fibronectin, insulin-like growth factor (IGF)-I, and matrigel. They also reduced cell motility and attenuated invasion potential, expressed by reduced secreted MMP-9 activity. These novel findings delineate the significance of CD81/CD82 expression to MM cell survival and their negative effects on cell adhesion, motility, and invasion thus, supporting their role as tumor metastasis suppressors.--Tohami T., Drucker L., Shapiro H., Radnay J., and Lishner M. Overexpression of tetraspanins affects multiple myeloma cell survival and invasive potential