Cellular Constituents of the Prostate Stroma: Key Contributors to Prostate Cancer Progression and Therapy Resistance

Reciprocal signaling between prostate stroma and its epithelium are fundamental to organ development and homeostasis. Similarly, interactions between tumor cells and stromal constituents are central to key aspects of carcinogenesis and malignancy growth involving tumor cell invasion, dissemination, and growth in distant sites. The prostate stroma is complex with several distinct resident cell types, infiltrating nonresident cell types and an amalgam of structural matrix factors, matricellular proteins, metabolites, growth factors, and cytokines. Of importance, the stroma is dynamic with changes in composition as a cause or consequence of intrinsic and extrinsic factors. In the context of epithelial neoplasia, the prostate stroma undergoes phenotypic changes with a loss of well-differentiated smooth muscle cell population and the expansion of cancer-associated fibroblast populations. This reactive stroma further coevolves with tumor progression. Recent studies show the role of tumor microenvironment components in therapy resistance and highlight the importance of a thorough knowledge of cross talk between tumor cells and microenvironment niches to develop new therapeutic strategies.