Breast Cancer Progression and Host Polymorphisms in the Chemokine System: Role of the Macrophage Chemoattractant Protein-1 (MCP-1) −2518 G Allele

Interaction between tumor cells and stroma is essential for tumor growth. Tumor cells stimulate the formation of stromal tissue, which excretes a variety of growth factors, cytokines, and proteases. Tumor-associated macrophages (TAMs) are one of the major components of tumor stromal tissue and are capable of eliciting diverse aspects of tumor growth as either a positive or negative regulator (1). In breast carcinoma, large numbers of infiltrating T cells and TAMs are often observed. The leukocyte infiltrate is found within the tumor stromal areas as well as in the epithelial areas that constitute the tumor mass (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Recent reports suggest that the inflammatory reaction at the breast tumor site affects tumor growth and progression. Whereas lymphocytes have been shown to have divergent effects on development of breast cancer (2)(10)(11)(12)(13), it is widely accepted that high concentrations of TAMs are correlated with poor prognosis (2)(3)(4)(5)(6)(7)(8)(9)(10). Macrophage infiltration into tumors is regulated by several cytokines and chemokines, in particular macrophage chemoattractant protein-1 (MCP-1). MCP-1 is a member of the C-C chemokine family and possesses chemotactic activity for monocytes and T lymphocytes (14)(15)(16)(17). MCP-1 is produced not only by tumor cells, but also by stromal cells such fibroblasts, endothelial cells, and monocytes. MCP gene transfer enhances the metastatic potential of cancer cells with increased neovascularization, whereas MCP-1 itself activates monocyte cytostatic function against tumor cells (18)(19). Recently, several studies have focused on other chemokines and chemokine receptors in the susceptibility and progression of cancer (20), in particular …