%0 Journal Article
%T £¿3 integrin modulates transforming growth factor beta induced (TGFBI) function and paclitaxel response in ovarian cancer cells
%A David A Tumbarello
%A Jillian Temple
%A James D Brenton
%J Molecular Cancer
%D 2012
%I BioMed Central
%R 10.1186/1476-4598-11-36
%X We have determined TGFBI signaling from the extracellular environment is preferential for the cell surface ¦Áv£¿3 integrin heterodimer, in contrast to periostin, a TGFBI paralogue, which signals primarily via a £¿1 integrin-mediated pathway. We demonstrate that suppression of £¿1 integrin expression, in £¿3 integrin-expressing ovarian cancer cells, increases adhesion to rTGFBI. In addition, Syndecan-1 and £¿4 expression is dispensable for adhesion to rTGFBI and loss of Syndecan-1 cooperates with the loss of £¿1 integrin to further enhance adhesion to rTGFBI. The RGD motif present in the carboxy-terminus of TGFBI is necessary, but not sufficient, for SKOV3 cell adhesion and is dispensable for adhesion of ovarian cancer cells lacking £¿3 integrin expression. In contrast to TGFBI, the carboxy-terminus of periostin, lacking a RGD motif, is unable to support adhesion of ovarian cancer cells. Suppression of £¿3 integrin in SKOV3 cells increases resistance to paclitaxel-induced cell death while suppression of £¿1 integrin has no effect. Furthermore, suppression of TGFBI expression stimulates a paclitaxel resistant phenotype while suppression of fibronectin expression, which primarily signals through a £¿1 integrin-mediated pathway, increases paclitaxel sensitivity.Therefore, different ECM components use distinct signaling mechanisms in ovarian cancer cells and in particular, TGFBI preferentially interacts through a £¿3 integrin receptor mediated mechanism to regulate the response of cells to paclitaxel-induced cell death.
%K Chemotherapy
%K Cell adhesion
%K Ovarian cancer
%K Integrin receptor
%K Extracellular matrix
%U http://www.molecular-cancer.com/content/11/1/36/abstract