Metastatic ability: adapting to a tissue site unseen

Abstract

The microenvironment of the primary as well as the metastatic tumor sites can determine the ability for a disseminated tumor to progress. In this issue of Cancer Cell, Calon and colleagues find that systemic TGF-β can facilitate colon cancer metastatic engraftment and expansion.

Figure 1. Scenarios for metastatic expansion

There are multiple possible mechanisms for metastatic progression. We assume that the rate limiting steps of metastasis do not necessarily involve the processes of tumor cell dissemination, but rather compatibility of tumor cells with their metastatic site. A. A primary tumor cell can acquire traits within the primary tumor that enable its progression in the metastatic site. B. Alternatively, the disseminated tumor cells that lodge in the metastatic site can lie ‘dormant’ until the new microenvironment potentiates the acquisition of traits that enable tumor progression. C. The work by Calon et al. (2012) suggest that elevated TGF-β and its downstream products induce changes in the microenvironment of the primary tumor and the metastatic site to facilitate metastatic progression. There are other possibilities mediating metastatic progression including variations and combinations of these three scenarios. The role of the immune system is not accounted for in this assessment.