Medical Research

Fred Hutchinson Cancer Research Center

Cyrus Ghajar, Peter Nelson, Patrick Paddison, Slobodan Beronja, Stephen Tapscott, Kirk Hansen
Seattle, WA
$1,000,000
June 2017

The majority of cancer metastasis research is focused on uncovering why certain organs (or “soils”) are permissive to colonization by tumor cells.  But why other tissues only very rarely succumb to metastasis is almost completely ignored.  Using skeletal muscle (SkM) as a model of infertile soil, a team of investigators at the Fred Hutchinson Cancer Research Center and at the University of Colorado, Denver proposes a series of experiments at the biological and technological cutting edge to specify the molecular mechanisms by which SkM suppresses metastasis.  Their goal is to test whether ectopic expression of SkM-derived metastasis suppressors prevents colonization of susceptible sites.  The team plans to: (1) identify metastasis suppressors within SkM; (2) reverse engineer growth resistance using rare tumor cells that successfully colonize SkM; and, (3) express SkM-derived factors specifically within the lungs of mice to determine whether this converts the lung from a metastasis-prone site to a metastasis-suppressive one.  The innovation of this work is the application of sophisticated models and techniques – including some pioneered by the team – to address a long-standing biological mystery: how SkM suppresses metastatic outgrowth. Solving this mystery could hold the key to creating a new paradigm in metastasis research; one that is based on defining the molecular nature of tissue-driven tumor suppression, and applying this information to convert fertile tissues into resistant ones.

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