Our Science – Yoshimura Website
Teizo Yoshimura, M.D., Ph.D.
Infiltration of leukocytes is a hallmark of inflammatory responses. It occurs in a number of human cancer and mouse cancer models. Although the exact role of tumor infiltrating leukocytes has not been completely understood, infiltrating leukocytes, such as tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) are generally immunosuppressive and provide a microenvironment that favors tumor growth. Therefore, identifying the mechanisms by which immunosuppressive leukocytes are recruited into tumors is critical and clinically relevant.
Monocyte chemoattractant protein-1 (MCP-1)/CCL2 is a chemokine that regulates the recruitment of monocytes into sites of inflammation and cancer. Accumulating evidence strongly suggest that the production of MCP-1 by tumors is responsible for the recruitment of immunosuppressive macrophages. In fact, recent studies demonstrated that neutralization of MCP-1 reduced the growth of prostate, breast and lung cancer in mice. Thus, MCP-1 is a molecular target of cancer treatment.
The role of MCP-1 in carcinogenesis was previously studied by others. In a chemically induced skin papilloma model, the number of papilloma in MCP-1-deficient mice was lower compared to that in wild-type mice. Recently, a vital role of MCP-1 in the initiation and progression of colitis-associated colon carcinogenesis was demonstrated by using CCR2-deficient mice and MCP-1 blocking agents. However, these studies were limited to defining the role for MCP-1 in cancer induction, and the role for this chemokine in later stages of tumor development, such as tumor growth and metastasis, remains unclear. To better define the role for MCP-1 in tumor growth and metastasis, I have generated systemic and conditional MCP-1-deficient mice.
In addition, we recently generated two new mouse models which are deficient in the classical chemoattractant receptors, formyl peptide rceceptor (FPR) 1 and 2, or cathelin-related antimicrobial peptide (CRAMP), a ligand for FPR2. A better understanding of the role of chemoattractants and chemoattractant receptors in cancer development may lead us to develop a novel strategy for cancer treatment.
This page was last updated on 7/10/2014.