Tumor cell receptor integrin avß3 increased the supply of VEGF when activated in the brain, reports study in PNAS.

Scientists from The Scripps Research Institute report finding a molecular mechanism that plays a role in controlling cancer growth in the brain. The study was published in this week’s online early edition of the Proceedings of the National Academy of Sciences. The paper is called “Activation of Tumor Cell Integrin avß3 Controls Angiogenesis And Metastatic Growth in the Brain.”

For tumor cells that have invaded the brain, the team found that when activated, a tumor cell receptor known as integrin avß3 increased the supply of VEGF, thus helping tumor expansion within the brain tissue through enhanced angiogenesis. They believe that activated avß3 promotes rapid tumor growth by enabling tumor cells to attract new blood vessels continuously, even when oxygen is still abundant.

In contrast, the same receptor did not influence tumor growth at the primary cancer site, in this case, the breast. This receptor’s varying effects on tumor cells depending on their location in the body reinforces a principle that this team uncovered a few years ago.

“For tumor cells, it’s not just the presence of the receptor on the cells but the conformation or shape of the molecule that determines how well tumor cells can do within different tissues,” explains Brunhilde Felding-Habermann, a research associate professor who led the study. “The shape of the molecule can increase or reduce the receptor’s affinity for its natural ligands.”

The scientists plan on following up on their new findings by testing if activated avß3 on tumor cells also supports brain metastasis of other types of cancer. They also intend on investigating if targeting the activated form of avß3 can inhibit metastatic brain disease.

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