Metastasis: inherent vs. acquired phenotype

Abstract

The problem how tumor cells get the metastatic ability is still a hot debate. Based on the premise that the default state of normal cells is quiescent rather than mobile, the classic progression and early metastasis model suggested that tumor metastasis should be an acquired trait contributed by the late or early gene mutations during carcinogenesis. Here, an inherent metastasis model is proposed that the metastatic ability of the tumor cells is one of the constitutive features of the normal cells of tumor origin. The idea is based on two facts. One is that tumor arises from stem or progenitor cells and in turn are driven by tumor stem cells. The other is that emerging evidence showing that a small population of stem or progenitor cells has the inherent migration capacity in normal development and adulthood. This inherent metastatic model has some implications. First, metastatic dissemination should occur continually throughout the course of primary tumor development and generate a diverse spectrum of disseminated cells. Second, most of the disseminated tumor cells should have the stem cell like features. Third, migration of stem cells and cancer cells should invoke similar molecular processes involving metastasis. Fourth, genomic alterations that primarily promote the production of tumor cells with stem cell traits, i.e., tumor stem cell, exacerbate tumor progression and metastasis. Finally, overt metastatic production is primarily determined by whether the disseminated tumor cells can survive and grow into overt metastatic foci at the ectopic sites, instead of that whether the tumor cells can leave the primary sites and travel to other sites. All these predictions have gotten increasing supporting evidences. Yet, to confirm whether the new paradigm is true or false, it needs carefully examine whether normal stem or progenitor cells of various tissues have the potential to traveling and arriving at the ectopic sites. Furthermore, exploiting the mechanisms for regulating normal stem or progenitor cells migration may provide more critical results for our deeply understanding the secrets of tumor metastasis and offer new methods for preventing and treating tumor metastasis.