PNAS paper describes observations that RhoC and VEGF must work together to allow intravasation.

Scientists at the University of California, San Diego School of Medicine report that they discovered two proteins that are both essential for the metastasis of breast cancer. 

The UCSD team developed an immuno-suppressed zebrafish that expresses green fluorescent protein only in its blood vessels, allowing scientists to view the tumor-induced angiogenesis. They injected the fish with inflammatory breast cancer cells that were tagged in different colors. 

The researchers found that both vascular endothelial growth factor (VEGF), a protein made by cancerous cells that stimulates angiogenesis, and RhoC, which is involved in cell movement or migration, cannot act alone but must interact for the cancerous tumor to enter the blood vessels.

The scientists explain 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 “in later stages of the cancerous tumor, VEGF induces rapid formation of irregular, leaky blood vessels,” says Konstantin Stoletov, Ph.D., at the department of pathology and first author of the paper. “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.”

The transparency of the fish also allowed the researchers to analyze images of a potential anticancer compound that inhibits the VEGF compound. They found that this inhibitor prevents formation of the vascular openings, thus inhibiting intravasation.

The study is published in the online October 22 edition Proceedings of the National Academy of Science.

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