REACTIVE STROMA IN PROSTATE CANCER PROGRESSION

Abstract

PURPOSE: The development of an altered stromal microenvironment in response to carcinoma is a common feature of many tumors. We reviewed the literature describing characteristics of reactive stroma, how reactive stroma affects cancer progression and how carcinoma regulates reactive stroma. Moreover, we present a hypothesis of reactive stroma in prostate cancer and discuss how the biology of reactive stroma may be used in novel diagnostic and therapeutic approaches. MATERIALS AND METHODS: An extensive literature search was performed to review reports of the general features of wound repair stroma, general stromal responses to carcinoma, and stromal biology of normal and prostate cancer tissues. These studies were analyzed and a reactive stroma hypothesis in prostate cancer was developed. RESULTS: Modifications to the stroma of breast, colon and prostate tumors parallel the generation of granulation tissue in wound repair. These changes include stromal cell phenotypic switching, extracellular matrix remodeling and angiogenesis induction. Therefore, it is predicted that a modified wound healing response induces the formation of reactive stroma in cancer to create a tumor promoting environment. Based on its role in wound repair and its over expression in prostate cancer, transforming growth factor-beta stands out as a potential regulator of reactive stroma. CONCLUSIONS: Reactive stroma in prostate cancer and granulation tissue in wound repair show similar biological responses and processes that are predicted to promote cancer progression. Further identification of specific functional and regulatory mechanisms in prostate cancer reactive stroma may aid in the use of reactive stroma for novel diagnostic and therapeutic approaches.