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Cell-To-Cell Communications in Cancer

Program Co-Leaders: Greg Longmore, MD, and Sheila Stewart, PhD

The goals of the new Cell-to-Cell Communications in Cancer (C4) Research Program are to bring together a wide variety of researchers that are committed to unraveling the complex tumor cell to cell and cell to environment communications (including interactions with stromal cells and the physical extracellular matrix) that are pivotal to cancer development, progression, and metastasis. Our membership includes individuals focused on understanding how the stromal cells; including non tumor epithelial cells, adipocytes, immune cells, vascular cells, and fibroblasts, and extracellular matrix structural proteins, growth factors, and cytokines interact with tumor cells to impact the tumorigenic process. The emphasis on communication is a key concept in cancer biology where all members have specific expertise and shared goals that will build the development of a program with strong and fruitful intra-programmatic and inter-programmatic interactions. It is now clear from work around the world that targeting tumor-stromal cell interactions is key to the development of effective therapeutic cancer treatments. The new C4 group is poised to add to this work.

The program is divided into three major themes of shared expertise and interests.

(1) Cytokine and Growth Factor signal transduction

This group has expertise in how cytokines and growth factors secreted by tumor and stromal cells signal within the tumor environment to control tumor cell proliferation (EGF, PDGF), survival (p53, apoptosis regulation), migration (G protein signal transduction), cell fate determination (Wnt, BMP, FGF), tumor initiating cell maintenance and expansion (Wnt, TGF), and inflammatory responses (chemokines, interleukins, TNF, NF-kB). These are critical regulators of communication between cells within the tumor microenvironment, between tumors and their metastatic niche, and control tumor cell trafficking and survival.

(2) Cell adhesion, invasion, and migration

This group has expertise in molecular and cell biology and biophysical properties that control tumor cell polarity, cell-cell and cell-matrix adhesion, cell movements with the tumor environment, and metastasis. Examples include the regulation of tumor and stromal cell cytoskeletal dynamics, the production and biochemical and biophysical function of tumor extracellular matrix (ECM), and how tumor cell – stromal cell interactions effect invasion and migration (e.g., epithelial-mesenchymal transitions EMT). These properties are particularly important in the understanding of tumor metastasis.

(3) Tumor and stromal cells  

This group has expertise in the function of various cell types within the tumor environment. Examples include immune cells, fibroblasts, adipocytes, endothelial cells, bone osteoclasts and osteoblasts. These cells contribute to senescence, fibrosis, and inflammation associated with tumorigenesis, and also how the immune system influences tumor progression. Within this group there is extensive expertise in genetically targeting these cells in vivo so as to determine their contribution to tumor development and progression. Understanding the source of these various cells and their function during tumorigenesis is critical for understanding cancer initiation, progression, and metastasis.