Tumor Macroenvironment: An Update.

Modes of tumor cell interaction include autocrine stimulation, secretion of paracrine growth factors and inhibitors, as well as interaction with the tumor macroenvironment. This evolving concept in tumor pathobiology describes the interaction of a malignant tumor with its host as an extension and addition to its local interaction with tumor cells and surrounding nontransformed cells, the tumor microenvironment. Angiogenesis, which is considered part of the tumor microenvironment, also allows reciprocal interactions between cancer cells and other organs and systems. Well-known examples of tumor endocrine signaling are the paraneoplastic syndromes. In addition, cachexia, a severe complication of tumor growth, results from the systemic reprogramming of the host metabolism as a result of tumor growth and progression. Moreover, recent reports indicate that cancer cells may secrete factors that might play a role in forming premetastatic niches at distant sites. In addition, cancer cells seem to be able to secrete factors influencing and resetting endogenous circadian organizers. The importance of understanding the whole complex interaction of a malignant tumor and its host - the tumor macroenvironment - is of great importance for the better management and treatment of cancer patients.