Role of inflammation-associated microenvironment in tumorigenesis and metastasis.

The tumor microenvironment contributes to every aspect of carcinogenesis and therefore offers promising targets for cancer therapy. Compared to chemotherapy alone, targeting tumor cells as well as key components of the tumor microenvironment significantly improve the clinical outcomes of patients. A better understanding of the interaction between tumor cells and the microenvironment could provide new therapeutic options and accelerate the development of novel anti-cancer drugs. In this review, we first defined the tumor microenvironment and then discussed the role of the tumor microenvironment in the initiation and progression of cancer focusing on three major pathways in a tumor cell life cycle: 1) growth and intravasation; in this section, the epithelial-mesenchymal transition (EMT), tumor cell migration, and tumor angiogenesis are reviewed. 2) dissemination; the activation and aggregation of platelets, as an important feature for the survival of tumor cells in the circulation, are reviewed under this section. 3) arrest, extravasation and growth at the secondary sites; the main contents of this section include tissue tropism in metastasis, the formation of the pre-metastatic niche, tumor cell adhesion and extravasation, the mesenchymal to epithelial transition (MET), and the formation of micrometastases and macrometastases. Finally, we briefly introduce the drug resistance mediated by the tumor microenvironment, and also summarize potential drug targets based on the current knowledge of the tumor microenvironment. Although the tumor microenvironment is equally important in the progression of carcinomas, leukemias, and sarcomas, in this review we focus on the common form of malignancy, carcinomas, which represent the malignancy derived from the epithelia.