Inflammatory breast cancer (IBC) is the deadliest form of human breast cancer, with fewer than half of those diagnosed today expected to live five years. The UCSD team developed an immuno-suppressed zebrafish that expresses green fluorescent protein (commonly known as GFP) only in its blood vessels, allowing scientists to view the tumor-induced blood vessel formation, or angiogenesis. They injected the fish with IBC cells that were tagged in different colors, in order to study the very rapid tumor progression.
The parental cancer cells were tagged in blue, and the migrating cells that overexpressed RhoC in red. Over several weeks, the researchers were able to watch the cancers progression using high-resolution, multi-color confocal microscopy.
The scientists discovered that RhoC induces an amoeboid-like mode of invasion, in which the cancerous cells move by means of temporary projections or false feet. They also found that secretion of VEGF was required in order for the cancer cells to penetrate and enter the blood vessel.
In later stages of the cancerous tumor, the VEGF induces rapid formation of irregular, leaky blood vessels, said Stoletov. We discovered that intravasation requires the secretion of VEGF, which disrupts the blood vessel wall, creating small openings that allow the tumor cells to penetrate and enter.
Finding a way to suppress VEGF, thus inhibiting the growth of leaky blood vessels, could stop the movement of cancer cells into the blood vessels and the tumors subsequent metastasis, according to Klemke.
The results provide novel insight into mechanisms of cancer-cell invasion and intravasation, showing how RhoC and VEGF cooperate to facilitate cell metastasis in living tissues. The transparency of the fish also allowed the researchers to image and analyze, in three dimensions, images of a potential anti-cancer compound that inhibits
|Contact: Debra Kain|
University of California - San Diego