Role of Tumor Microenvironment and the FGF Signaling Axis on Differentiation and Emergence of the Neuroendocrine Phenotype in Prostate Cancer

摘要

Specific changes in the fibroblast growth factor (FGF) signaling axis can abrogate stromal-epithelial interactions to modify the microenvironment of the prostate gland. We have previously demonstrated that signaling through ECK receptor 1 (FGFR1) but not FGFR2 promoted emergence of epithelial to neuroendocrine transition (ENT). We have established protocols to introduce constitutively active receptors in prostate epithelial cells and measure expression of genes associated with epithelial (E-cadherin), stromal (Cadherin- 11), neuronal (N-cadherin), angiogenic (VE-cadherin), and neuroendocrine (neuron-specific enolase, chromogranin A, and synaptophysin) phenotypes using Real-Time PCR. In determined that TRAMP-C2H, known to be tumorigenic and metastatic, express high levels of FGFRliiic in contrast to ClA cells that are not tumorigenic. Consistent with clinical data C2H cells express very low levels of E-cadherin.