Integrin Activation in the Metastasis of Breast Cancer

Institution: The Burnham Institute for Medical Research
Investigator(s): Emme Lin, Ph.D. -
Award Cycle: 1997 (Cycle III) Grant #: 3FB-0085 Award: $264
Award Type: Postdoctoral Fellowship
Research Priorities
Biology of the Breast Cell>Pathogenesis: understanding the disease

Initial Award Abstract (1997)
In breast cancer, the most dangerous stage of the disease is when the tumor cells spread (metastasize) to other areas of the body. When this happens, the chance for survival is decreased because tumor invasion can be very widespread. Integrins are proteins on the cell surface that are involved in cellular adhesion functions necessary for attachment and movement. Cells have several integrins on their surface, and the presence and role of specific integins in tumor metastasis is not clear. The focus of our research is on a specific integrin receptor, called avb3. In previous work we have found that it is present at higher levels in breast cancer tumors that are metastatic. We showed direct evidence that avb3 is necessary for the invasion of breast cancer.

Our research has two objectives. First, we propose to strengthen the observation on the essential role of avb3 in metastasis. For these experiments we will use mutant forms of avb3 and examine the ability of cells to form tumors in mice. Secondly, we will test the hypothesis that the cell adhesion function of avb3 is regulated by an "On/Off switch" that operates within the cell. Our hypothesis is that when avb3 is "on," the cell will bind tightly to its surroundings such that the cell is immobilized. Conversely, when avb3 is "off," the tumor cell can "walk away" and spread to other areas of the body. Normal cells can regulate the "On/Off switch," so that the avb3 function becomes modulated. Thus, tumor cells gain the ability to invade because they can no longer control the "On/Off switch." Our approach will be to (i) develop antibodies to "freeze" the avb3 integrin receptor in a state to prevent metastasis and (ii) study a possible regulatory protein for the "On/Off switch." The regulatory protein is apparently absent in tumor cells, which allows them to spread. We will test this by introducing this regulatory protein into tumor cells to determine whether metastasis is affected.

These studies will possibly provide new breast cancer therapeutic targets (the "On/Off switch" and its regulators) for designing drugs to halt the spread of breast cancer.

Final Report (1999)
The project was canceled when the PI resigned.