The Role of Myofibroblasts in Communicating Tumor Ecosystems
Invasive growth of a tumor occurs within an ecosystem where a continuous communication exists between cancer cells and a wide network of tumor-associated host cells. Secretory factors from the cancer cells activate the recruitment of host cells, both near to and far from the primary tumor site, as well as promote the departure of cancer- and host cells to distant tissues. The present review focuses on the prominent role of myofibroblasts in local and distant ecosystems namely the primary tumor, the bone marrow, the circulation, the sites of lymph node and of distant metastases and the nervous system. We believe that there exist distinct types of myofibroblasts with distinct reaction patterns that affect invasive tumor growth in different ways. Mathematical models predict that the specific conditions in local ecosystems determine the invasive phenotype of a tumor. Experimental cell culture models incorporating cancer cells, primary tumor-derived myofibroblasts and matrix proteins in a three-dimensional context confirm the pro-invasive activity of myofibroblasts. New methodologies will facilitate the direct observation of invasive cells including their interaction with myofibroblasts in clinically relevant ecosystems. A better understanding of the local and distant tumor ecosystems may help us to design personalized strategies in the treatment of cancer.
KeywordsCollective Cell Migration Premetastatic Niche Invasive Tumor Growth Stromal Myofibroblasts Cancer Cell Spheroid
This work was supported by Fund for Scientific Research-Flanders (Brussels, Belgium), O. De Wever is a post-doctoral researcher and A. De Boeck is a doctoral researcher supported by Fund for Scientific Research-Flanders.
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