DF/HCC Program Affiliation

Gastrointestinal Malignancies

Research Abstract

Cancer cells interact with surrounding stromal fibroblasts during tumorigenesis, but the complex molecular rules that govern these interactions remain poorly understood thus hindering the development of therapeutic strategies to target cancer stroma. We have taken a mathematical approach to begin defining these rules by performing the first large-scale quantitative analysis of fibroblast effects on cancer cell proliferation across more than four hundred heterotypic cell line pairings. Systems-level modeling of this complex dataset using singular value decomposition revealed that normal tissue fibroblasts variably express at least two functionally distinct activities that can act coordinately or at cross-purposes to modulate cancer cell proliferation. These findings suggest that quantitative approaches may be useful for identifying organizational principles that govern complex heterotypic cell-cell interactions in cancer and other contexts.

Publications

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