Einstein Researchers Discover Protein that Contributes to Cancer Spread
News Dec 18, 2008
In an important finding published online in Developmental Cell, researchers at Albert Einstein College of Medicine of Yeshiva University, along with collaborators at Massachusetts Institute of Technology, have identified a protein likely responsible for causing breast cancer to spread.
Metastatic cancer occurs when cancer cells from the original tumor travel to distant sites via the bloodstream. Most cancer deaths occur when cancer spreads to other organs. Trying to stop cancer before it metastasizes is the main goal of cancer treatments.
A marker showing that cancer has spread would help doctors choose the best possible treatment options for patients. Upon diagnosis, 6 out of 10 breast cancer patients have cancer that is still in its primary location making the potential discovery of a marker for invasive cancer of tremendous value.
Early markers of metastatic breast cancer have been hard to find. In the Einstein-led study, researchers have identified a protein that is a promising candidate for a metastatic breast cancer marker.
The protein, called Menainv is present in invasive cells within a breast tumor. These cells move into surrounding tissue and eventually to blood vessels. Menainv is not found in cells that stay within breast tumors, an indication that this protein contributes to the invasive and metastatic ability of tumor cells and is not just an 'innocent bystander'.
The research was conducted under the direction of John S. Condeelis, Ph.D., professor and co-chair of anatomy and structural biology at Einstein and co-director of the Gruss Lipper Biophotonics Center and Frank B. Gertler, Ph.D., Ross Scholar Professor of Biology at MIT.
The latest research was aided considerably by the work of Jeffrey B. Wyckoff, principal associate of anatomy and structural biology at Einstein who, with Dr. Condeelis, developed the in vivo invasion assay used to isolate metastatic tumor cells from breast tumors thereby implicating Menainv as important for metastasis.
Evanthia T. Roussos, an M.D.-Ph.D. student in Dr. Condeelis' lab and primary co-author of the study, explains, "We have micro-needles filled with growth factors and tissue that we insert into a tumor on an anesthetized mouse. If a tumor cell is invasive, within four hours, it will crawl into the needles. We found that mouse breast tumor cells that we engineered to contain Menainv were invasive whereas cells that did not have Menainv were not."
The study also found that tumor cells harboring Menainv are less likely to be responsive to newer breast cancer treatments that inhibit epidermal growth factor receptors (EGFR). Epidermal growth factor (EGF) has been shown to increase a breast cancer cell's invasive potential.
Drugs that inhibit EGF may lack effectiveness against tumor cells that express Menainv. That's because Menainv cells are so sensitive to EGF that even the small amount of EGF signal that the drugs fail to block may be enough to stimulate EGF receptor and promote tumor cell migration and metastasis.
If Menainv behaves in humans the way it does in mice, researchers could develop an antibody test or PCR assay to identify it.
The current study builds on previous research by Dr. Condeelis' group which identified Menainv as the isoform of Mena that is over-expressed in the invasive and metastatic subpopulation of tumor cells in breast tumors. The current study shows that Menainv forces tumor cells in mammary tumors of mice to become invasive and eventually metastasize to the lung.