Mutual cytokine crosstalk between colon cancer cells and microenvironment initiates development of distant metastases.

Abstract

Tumor growth and cancer development are considered clear examples of Darwinian selection, whereby random mutational events in heterogeneous cancer cell populations that best fit the selective microenvironment are preferred.(1) As a result, cancer cells evolve resistance to apoptosis, hide from immune surveillance and acquire the ability to invade other organs. Cancer cells, however, are not necessarily passive subjects of selection; they can actively subvert the host tissue to provide a favorable habitat for their growth. Recent findings by Calon et al. convincingly demonstrate that transforming growth factor-β-induced secretion of interleukin 11 by tumor stromal fibroblasts is a necessary prerequisite for the development of distant metastases in colorectal carcinoma. Thus, understanding the complex molecular feedback loops between cancer cells and the surrounding microenvironment (i.e., the tumor-associated stroma or invaded host tissue) should aid the identification of useful molecular targets for improving clinical management of advanced metastatic cancers.