Bruce E. Elliott, Ph.D.
Office Phone: 613-533-2825Fax: 613-533-6830
- Professor of Pathology & Molecular Medicine, Oncology, and Microbiology & Immunology
- BSc, MSc, PhD, Queen's University
Dr. Elliott's Lab
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Stromal-tumour Tissue Interactions in Breast Cancer Metastasis
Both extracellular matrix and growth factors are important regulators of stromal-tumour cell interactions in mammary tumour progression (Figure 1). We have shown that platelet-derived growth factor (PDGF) beta-receptor is expressed in the peri-epithelial stroma (especially vascular endothelia) of human breast carcinomas in situ (Figure 2), suggesting a role of PDGF in angiogenesis during early tumour development. We have also shown that over-expression of hepatocyte growth factor (HGF) and its receptor, Met, occurs in regions of invasive human breast carcinoma (see Growth Factors, Figure 3). These findings suggest that autocrine HGF/Met signalling is linked to mammary tumour progression, and may identify a high risk breast cancer subgroup. In a complementary approach, we have demonstrated a novel interaction between Met and cell adhesion (integrin) signalling cascades, which promote tumour invasiveness (See Cell Adhesion, Figure 8). Interactions of Met with Src tyrosine kinase and the actin cytoskeleton are critical for this process. Thus both ligand-dependent and ligand-independent pathways can affect Met activation and function in mammary tumourigenesis. Understanding these mechanisms could provide clues to new approaches for early detection and treatment of metastatic breast cancer.
Figure 1. The mammary gland provides a specialized tissue environment for growth and differentiation of mammary neoplasia: Recent evidence suggests that extracellular matrix (ECM) and growth factors are important regulators of stromal-tumor cell interactions in mammary tumor progression
Figure 2. Photomicrograph of a human mammary ductal carcinoma in situ stained for PDGF beta-receptors in the stroma and cytokeratin in carcinaoma cells.