Abstract 1546: CD44 cleavage promotes anoikis resistance in oral squamous cell carcinoma

Abstract Background: CD44, a cell surface proteoglycan receptor, plays an important role in modulating oral squamous cell carcinoma (OSCC) cell functions. The recent identification of CD44 as a cancer stem cell marker led us to hypothesize that cleavage of CD44 may alter OSCC cell-matrix interactions and anoikis resistance, and thereby promote a metastatic phenotype in OSCC. Methods: Anoikis-resistant cells were developed by maintaining human OSCC (UM-SCC 14A) cells under suspension culture conditions in polyhydroxyethylmethacrylate (poly-HEMA) coated plates. Anoikis sensitive control cells were maintained in adherent culture conditions. CD44 cleavage was blocked by the use of matrix metalloproteinase (MMP) chemical inhibitors, including ADAM-17 and ADAM-10. Western blot analysis was used to examine the relative levels of CD44 among the adherent and anoikis-resistant cells. Results: This study showed that anoikis resistant OSCC cells exhibit higher levels of CD44 cleavage than their adherent counterparts. The study also showed that ADAM-10 and ADAM-17 chemical inhibitors blocked CD44 cleavage and the formation of anoikis-resistant multicellular aggregates in OSCC cells. Conclusions: CD44 cleavage plays a crucial role in promoting the anoikis resistant phenotype in OSCC cells, suggesting that CD44 may significantly contribute to OSCC tumor initiation and metastasis. (Supported by NIH RO1 DE014429 to YLK) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1546. doi:10.1158/1538-7445.AM2011-1546