Cancer Biology Professor Receives VA Merit Grant for Continuing Breast Cancer Research

Susan Waltz, PhD, professor in the Department of Cancer Biology and member of both the Cincinnati Cancer Center and UC Cancer Institute, received a U.S. Department of Veterans Affairs (VA) Merit Grant, totaling over $1 million ($1,029,228) over the next four years, to continue research on the function of the Ron receptor tyrosine kinase in breast cancer.  

The Ron receptor sits on the outside of cells and works to provide communication between them. Waltz says that the Ron receptor is overproduced (overexpressed) in about half of breast cancers and that overexpression is linked to increased tumor spread (metastasis) and poor outcomes.  

"Breast cancer is the most common cancer in women and is the second-leading cause of cancer death in the U.S.," Waltz says. "As breast cancer incidence and death rates increase with age, the prevalence of breast cancer and illness-related deaths are likely to increase with the aging veteran population, and in correlation, the Veterans Administration's expenditures and care for patients with this disease will also increase.

"While significant efforts and advancement into the treatment of this disease have occurred at the VA and in other institutions, a significant gap still exists in our ability to effectively treat patients with aggressive and metastatic breast cancer. In this study, we hope to use the Ron signaling pathway as a biological marker of aggressive disease and potential new therapeutic target to combat breast cancer growth and spread by affecting both the tumor and using immune responses."

The Merit Grant is a continuation of Waltz's previous VA funding, during which her lab developed a specific animal model to study the role of Ron expression in breast cancer. Using this unique model, Waltz was the first to show that overexpression of the Ron receptor in animals is enough to drive breast tumor formation and tumor spread, similar to the aggressive disease seen in some women.  

"While Ron overexpression is an important factor, we still don't know much about the mechanisms by which Ron promotes the development of aggressive disease," says Waltz.

Work from the previous grant also showed the molecule that activates the Ron receptor, hepatocyte growth factor like protein (HGFL), is also important for cancer formation.  

"When HGFL is not present in the animal model, it takes longer to develop tumors and have fewer metastases," Waltz says, adding  that using breast tumor cells without HGFL, her lab has shown that providing HGFL back to the cells promoted tumor cell survival, movement and invasion as well as changes in the tumor's environment.  

"We propose that tumor cell produced HGFL promotes aggressive breast cancer through the activation of Ron signaling within the tumor's environment, leading to increased tumor growth and reduced tumor killing by the immune system," she says. "We're grateful for this award which will hopefully help us understand the role of HGFL-Ron signaling in the development and spread of breast cancer and provide a rationale for the development of new diagnostic or treatment options."

Co-investigators on the study include Elyse Lower, MD; Nira Ben-Jonathan, PhD; Fred Finkelman, MD; Bruce Aronow, PhD; Margaret Collins, MD; Nancy Benight, PhD; Viji Vummidi-Premkumar, PhD; and Sasha Ruiz-Torres (graduate student).