Researchers unravel important role of Rb tumor suppressor in aggressive form of breast cancer

December 4, 2013, University of Cincinnati Academic Health Center

The retinoblastoma (Rb) protein plays a critical role in suppressing the multi-step process of cell migration through the bloodstream, lymphovascular invasion and the metastasis of an aggressive type of breast cancer to the lung, researchers at the University of Cincinnati (UC) Cancer Institute, the Cincinnati Cancer Center (CCC) and the UC Brain Tumor Center have found.

The findings of Rb's role at multiple points in the disease process point to a potential new therapeutic target in patients with the most aggressive subset of breast , known as basal-like breast carcinomas. This type of cancer has no estrogen receptor expression, and to date there is no efficient therapy for patients who suffer from it, leaving them with a generally poor prognosis. Basal-like breast carcinomas spread to the lungs in about 25 percent of cases and to the brain in about 30 percent of cases.

The findings are published online in the journal PLOS ONE. The investigator-initiated research was funded by the UC Department of Cancer Biology's Startup Fund, the UC Dean's Fund and the Mayfield Education and Research Foundation.

"Our research suggests that Rb inhibits collective , which in turn inhibits the lymphovascular invasion, the release of cancer cells into the blood circulation and the growth of metastasis," says Samuel Godar, PhD, who led the study while an assistant professor in the Department of Cancer Biology. Godar is now visiting assistant professor of at UC and president of BioTest4U, a biotech startup based in Loveland, Ohio, and Covington, Ky.

The deadly progression begins when decreased levels of Rb are coupled with an increase in the expression of an oncoprotein (a gene that has the potential to cause cancer) called CD44. Basal-like breast carcinomas are known to have an elevated expression of CD44 and relatively low levels of Rb. Expression of the oncoprotein CD44 is required for the cells to move actively through the bloodstream.

The researchers studied Rb in two different ways. They studied its ability to suppress collective cell migration in cultures at the Vontz Center for Molecular Studies. They also studied Rb in an animal model, examining its ability to suppress the release of single and cancer cell clusters into the bloodstream.

"Our results suggest that Rb suppression stimulates an array of pathological consequences," says co-investigator James Driscoll, MD, PhD, assistant professor in the UC Department of Internal Medicine's Division of Hematology Oncology and member of the CCC. "It stimulates collective rather than single cell-based invasion and migration; it leads to lymphovascular invasion; and it orchestrates metastasis to remote organs through the bloodstream."

The research illuminates the crucial role of the Rb/CD44 pathway in the metastatic progression of basal-like breast carcinomas, Godar says.

"It points to the Rb/CD44 pathway as a promising target for therapy to combat the propensity for these aggressive breast cancers to metastasize to the lung and brain. About 90 percent of cancer patients die primarily because of metastatic disease. We believe that the complex analysis of metastatic progression in a preclinical model, such as the analysis we used, will become essential for predicting the true powers of novel anti-cancer drugs."

Explore further: Breast cancer patients who lack RB gene respond better to neoadjuvant chemotherapy

More information: dx.plos.org/10.1371/journal.pone.0080590

Related Stories

Breast cancer patients who lack RB gene respond better to neoadjuvant chemotherapy

July 26, 2012
Breast cancer patients whose tumors lacked the retinoblastoma tumor suppressor gene (RB) had an improved pathological response to neoadjuvant chemotherapy, researchers at Thomas Jefferson University Hospital and the Kimmel ...

New study shows insight into breast cancer cell migration

October 29, 2013
(Medical Xpress)—A new study by University of Kentucky Markey Cancer Center researchers Min Chen and Kathleen O'Connor shows that a specific protein may assist breast cancer cells in metastasizing.

Obesity found to be major risk factor in developing basal-like breast cancer

November 18, 2013
Women who are obese face an increased risk of developing an aggressive sub-type of breast cancer known as 'basal-like', according to research conducted at the University of North Carolina.

SABCS: Loss of RB in triple negative breast cancer associated with favorable clinical outcome

December 9, 2011
Researchers at the Thomas Jefferson University Hospital and Kimmel Cancer Center at Jefferson have shown that loss of the retinoblastoma tumor suppressor gene (RB) in triple negative breast cancer patients is associated with ...

Team finds potential cause for deadly breast cancer relapse

November 25, 2013
Researchers at the UNC School of Medicine, working with cell lines in a lab, have discovered why some of the most aggressive and fatal breast cancer cells are resistant to chemotherapy, and UNC scientists are developing ways ...

Researchers find potential target for treating metastatic cancer

December 13, 2011
Finding ways to counteract or disrupt the invasive nature of cancer cells, called "metastasis," has been a long-term goal of cancer researchers. Now, researchers at Moffitt Cancer Center in Tampa, Fla., have identified an ...

Recommended for you

Modular gene enhancer promotes leukemia and regulates effectiveness of chemotherapy

January 18, 2018
Every day, billions of new blood cells are generated in the bone marrow. The gene Myc is known to play an important role in this process, and is also known to play a role in cancer. Scientists from the German Cancer Research ...

Researchers find a way to 'starve' cancer

January 18, 2018
Researchers at Vanderbilt University Medical Center (VUMC) have demonstrated for the first time that it is possible to starve a tumor and stop its growth with a newly discovered small compound that blocks uptake of the vital ...

Researchers develop swallowable test to detect pre-cancerous Barrett's esophagus

January 17, 2018
Investigators at Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center have developed a simple, swallowable test for early detection of Barrett's esophagus that offers promise ...

Scientists zoom in to watch DNA code being read

January 17, 2018
Scientists have unveiled incredible images of how the DNA code is read and interpreted—revealing new detail about one of the fundamental processes of life.

Presurgical targeted therapy delays relapse of high-risk stage 3 melanoma

January 17, 2018
A pair of targeted therapies given before and after surgery for melanoma produced at least a six-fold increase in time to progression compared to standard-of-care surgery for patients with stage 3 disease, researchers at ...

Dulling cancer therapy's double-edged sword

January 17, 2018
Researchers have discovered that killing cancer cells can actually have the unintended effect of fueling the proliferation of residual, living cancer cells, ultimately leading to aggressive tumor progression.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.