Overexpression of tetraspanins affects multiple myeloma cell survival and invasive potential

Tali Tohami, Liat Drucker, Hava Shapiro, Judith Radnay, Michael Lishner

Research output: Contribution to journalArticlepeer-review

Abstract

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, insulinlike 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.

Original languageEnglish
Pages (from-to)691-699
Number of pages9
JournalFASEB Journal
Volume21
Issue number3
DOIs
StatePublished - Mar 2007

Keywords

  • CAG
  • CD81
  • CD82
  • RPMI 8226

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