Tumor microenvironment promotes cancer progression, metastasis, and therapeutic resistance

The homeostatic status of cellular tissue results from a dynamic balance of cell proliferation, differentiation, and apoptosis. These unique organ-specific phenotypes are conferred and maintained by interaction between epithelium and adjacent stroma through intimate intercellular signaling pathways. Similarly, the tumor microenvironment, or stroma, influences tumor growth, progression, and metastasis. It also can limit the access of therapeutics to the tumor, alter drug metabolism, and contribute to the development of drug resistance. Because of their role in all stages of tumor development, stromal elements are attractive therapeutic targets. Manipulating host-tumor interactions may be important for preventing or reverting malignant conversion and re-establishing normal control mechanisms. Our research priorities include a better understanding of tumor microenvironments, the identification and characterization of the signatures of seemingly normal cells within the tumor microenvironment and signatures that reflect changes that occur as cancer cells interact with the host microenvironment, and molecular mechanisms that can be exploited as therapeutic strategies. These goals can be expedited by encouraging interdisciplinary research teams and multi-institutional collaboration. Crucial advances in technology have been critical for progress, to include: (1) novel in vitro 3D matrix reconstitution and organotypic models, and animal models; (2) techniques such as laser capture microscopy for the isolation and characterization of stromal cells; and (3) the discovery of novel stromal markers through molecular profiling and their application for the development of reagents for in vivo imaging to visualize tumor-host interactions. These technologies will provide the tools for a better understanding, of the tumor microenvironment and the development of tissue- or cell-specific targeting agents. Successful targeting can have dramatic effects making the tumor microenvironment hostile to the tumor, thereby transforming cancer into a chronic, but benign disease. In this review, we mainly focus on prostate cancer tumor-stroma interaction with discussion of stromal effects on other solid tumors.