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Breast cancer patients do not die from their tumor as long as it stays in the breast. Rather, it is the metastatic disease, tumor that spreads beyond the breast, that results in the death of over 40,000 women and men in the United States each year. Dan Welch’s lab at the University of Kansas studies a key step in the development of metastatic disease. In order for a metastatic tumor to grow, tumor cells must break apart from the primary tumor, travel to a distant site, and then find a hospitable place where they grow and form a new tumor. Realizing that upon diagnosis, cells from the tumors of many early stage patients may have already begun their journey throughout the body, and that these cells are not harmful to a patient until they begin to colonize (i.e., grow in) a distant organ, Dr. Welch’s lab is looking at how to prevent the colonization of these tumor cells. The KISS1 gene was originally found on a portion of chromosome 6 which is frequently altered in melanomas. In mouse models that lack a functional KISS1 protein, while a primary tumor could continue to grow, new metastatic sites would not develop. The Welch lab has subsequently determined that KISS1 suppresses metastasis in many cancer types, including breast and prostate. But more importantly, Dr. Welch and his team determined that the role of KISS1 was to suppress the colonization of new metastatic sites. Unfortunately, the mechanism by which suppression of colonization occurs has been more difficult to determine. The Metavivor grant allowed Dr. Welch and his lab to generate the tools and the data necessary to secure a prestigious RO1 grant from the National Institutes of Health to continue to characterize KISS1 and its role in suppressing metastatic colonization, with the ultimate goal of using that information in the development of an anti-metastasis therapeutic.
Of course, no one wants to think that tumor cells may be floating around in their bodies, just looking for a spot to colonize. But the tumor cells that are only floating around aren’t the ones that kill a patient. The cells that the patient needs to worry about are the ones that find a home and start to grow, taking over a vital organ until it can no longer function. Understanding that the time of diagnosis is often too late to treat a patient with a strategy to prevent cells from escaping the tumor, Dr. Welch is targeting the tumor cells at the last, but crucial, step: colonization. If a protein could be developed that could be given to a patient, much like insulin is given to diabetics whose body doesn’t make sufficient levels of that protein, it could stop tumor cells from ever colonizing a distant organ, and prevent the metastatic disease that claims the life of breast cancer patients.