The tumor microenvironment: key to early detection.

The tumor microenvironment plays an important role equal to the tumor cell population in the progression of cancer. Consisting of stromal fibroblasts, inflammatory cells, components of the vasculature, normal epithelia, and extracellular matrix, the surrounding environment interacts or "cross-talks" with tumor cells through the release of growth factors, cytokines, proteases, and other bioactive molecules. Tumor growth, formation of new vascular networks, evasion of the host immune system, and invasion and metastasis are processes that co-evolve and become finely optimized and regulated within the tumor microenvironment. However, relatively recent reports on three areas of study have come together to add new levels of complexity to the tumor microenvironment. These include ectodomain shedding of proteins, shedding of membrane-derived vesicles, and novel roles for phospholipids. These dynamic changes that take place in the tumor microenvironment provide new avenues for study and for the early detection of cancer, whereas proteomic technologies provide the means to detect these unique proteins and lipids. Here we review the evolving concepts of the tumor microenvironment that, together with advances in proteomic technologies, hold the promise to facilitate the detection of early-stage cancer.