Abstract 5188: Altering cell attachment to growth substrate up-regulates growth differentiation factor 15 (GDF15) expression

Abstract

Abstract Cell attachment to the extracellular environment is critical in determining cell fate. When normal cells lose attachment, they undergo anoikis. Cancer cells develop resistance to anoikis which results in metastasis. While there are many known genes alterations that can alter cell adhesion, less is known about how such a loss of cell adhesion may influence gene expression. We believe that a change in cell adhesion could trigger changes to gene expression, and the resulting changes play an important role in prostate cancer metastasis. Using prostate cancer cell lines, we examined gene expression changes in cancer cells brought about by loss of attachment to their growth substrate through chemical and physical means and how these changes play a role in prostate cancer. Microarray analysis was performed on LNCaP cells treated with latrunculin B, an actin cytoskeleton disrupting agent for 8 hours. Using quantitative real time PCR and immunoblot analysis, a member of the tumor growth factor beta superfamily, GDF15 was found to be consistently up-regulated when the cells were treated with either latrunculin B or other drugs that disrupt the actin cytoskeleton. These findings were observed not only in LNCaP but in PC3 and DU145 as well. GDF15 expression was rapidly increased in these three cell lines when cells were prevented from attaching to tissue culture plastic and the levels of GDF15 expression could be maintained as long as the cells were not allowed to re-attach. This up-regulation was reversed when cells were allowed to re-attach to growth substrate, or by regaining cell shape when the drugs were removed. GDF15 has been shown to be associated with metastatic prostate cancer as well as contributing to disease associated cachexia. In our study, we demonstrated that loss of cell adhesion was sufficient to increase GDF15 expression in a rapid and sustainable manner. This finding is novel and different from other reports that increased GDF15 led to altered cell shape and adhesion. We believe that our findings may provide a picture of the initial stages in metastasis when a cancer cell loses adhesion to the extracellular environment. Furthermore, our results reinforce the potential utility of GDF15 as a prognostic marker in prostate cancer, as well as the intricate relationship between the cell and the physical environment in cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5188. doi:1538-7445.AM2012-5188