A well-known marker of metastatic breast cancer and melanoma may also indicate aggressive head and neck cancer and offer an important new therapeutic target, according to a new study led by researchers at the Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute.
Overexpression of the gene RhoC is associated with invasive breast cancer, with progression to invasive disease in several cancer types, and with conversion of immobile breast epithelial cells into highly mobile, invasive cells.
This laboratory and animal study suggests that inhibiting RhoC function in head and neck squamous cell carcinoma (HNSCC) reduces a tumor’s aggressive behavior and identifies the RhoC pathway as a target for HNSCC therapy.
The findings, published and highlighted in the November issue of the journal Molecular Cancer Research, suggest the following:
•That RhoC plays an important role in cell invasion, motility and metastasis in HNSCC;
•That inhibiting RhoC expression reduces lung metastasis in an animal model;
•That RhoC is required for formation of tumor blood vessels.
“Our findings illustrate the important role of RhoC in head and neck cancer progression and metastasis and suggest that this protein may be a novel target for therapeutic intervention,” says study leader Dr. Theodoros N. Teknos, professor of otolaryngology, director of head and neck oncologic surgery, and the David E. and Carole H. Schuller Chair in Head and Neck Oncologic Surgery.
Head and neck cancer is the sixth most lethal cancer worldwide, and about 70,000 new cases of HNSCC are expected in the United States this year.
Most cases of HNSCC are diagnosed at a late stage, which diminishes the chance for cure, Teknos says. Despite advances in surgery, chemotherapy and radiation therapy survival rates have remained largely unchanged for several decades. The main cause of mortality is recurrent disease that arises locally, regionally and at distant sites as a consequence of metastasis.
Teknos and his colleagues used RNA silencing techniques to reduce RhoC expression by 70 to 80 percent in several aggressive HNSCC cell lines. The modified cells were significantly less motile and invasive in laboratory assays, and they showed a marked drop in ability to form lung tumors in an animal model compared with the original cell lines.
Funding from the National Cancer Institute Head and Neck Cancer Specialized Programs of Research Excellence, Breast Cancer Research Foundation and Burroughs Wellcome Fund supported this research.
Other researchers involved in this study were Mozaffarul Islam, Quintin Pan, Yanjun Hou and Pawan Kumar of Ohio State University; and Giant Lin, John C. Brenner and Sofia D. Merajver of the University of Michigan.
The Ohio State University Comprehensive Cancer Center- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute is one of only 40 Comprehensive Cancer Centers in the United States designated by the National Cancer Institute. Ranked by U.S. News & World Report among the top 20 cancer hospitals in the nation, The James (www.jamesline.com) is the 180-bed adult patient-care component of the cancer program at The Ohio State University. The OSUCCC-James is one of only five centers in the country approved by the NCI to conduct both Phase I and Phase II clinical trials.