Overexpression of tetraspanins affects multiple myeloma cell survival and invasive potential.
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
Tali
T
Oncogenetic Laboratory, Meir Medical Center, Kfar Saba 44281, Israel.
Drucker
Liat
L
Shapiro
Hava
H
Radnay
Judith
J
Lishner
Michael
M
D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D009101:Multiple Myeloma / Q000473:pathology*; D009361:Neoplasm Invasiveness; D059470:Tetraspanins; D014407:Tumor Cells, Cultured
D008565:Membrane Proteins; D059470:Tetraspanins; C435756:Tspan5 protein, mouse