The microenvironment of the
cancer cell is pivotal to its phenotypic regulation. One of the central components of the microenvironment is temperature. An elevation in environmental temperature has been shown to increase the
cancer cell's susceptibility to chemo- and
radiation therapy. The goal of the studies described here was to identify some of the pathways that are modified by a mild increase in temperature in
cancer cells. Using
prostate cancer cells as a model system we found that in addition to the well described and anticipated up-regulation of the heat shock family of
proteins, there is a significant down-regulation of certain members of the "cold shock" family of
proteins such as, RNA binding motif
protein 3 (RBM3) and cold inducible
RNA binding protein (CIRBP).
siRNA-mediated down-regulation of the
cold shock protein (CSP) encoding mRNAs dramatically attenuates cell survival in the absence of any heat application. Furthermore, we also demonstrate that knocking down the CSPs can enhance the therapeutic response of
prostate cancer cells to
chemotherapy. Our findings suggest that down-regulating CSPs in
cancer cells may "mimic" the stress response the cells experience when exposed to heat treatment rendering them more susceptible to
therapy. Thus, the pharmacological modulation of RBM3 and CIRBP may represent novel therapeutic approaches for
prostate cancer.