Washington, June 9 (ANI): In what may become a new drug target for metastatic brain cancer, scientists from The Scripps Research Institute have discovered a molecular mechanism that plays a pivotal role in controlling cancer growth in the brain.
“Our study could have a broad impact because it explains at a molecular level how metastatic lesions thrive in the brain. This offers a potential target for inhibiting the growing problem of brain metastasis,” said Scripps Research Associate Professor Brunhilde Felding-Habermann, who led the study published in an online Early Edition of the journal Proceedings of the National Academy of Sciences (PNAS).
She has found that for tumour cells that have invaded the brain, a tumour cell receptor known as integrin avß3 increased the supply of a growth factor involved in the development of new blood vessels (“angiogenesis”) necessary for tumour expansion within the brain tissue.
In contrast, the same receptor did not influence tumour growth at the primary cancer site, in this case, the breast.
“The fact that we uncovered a link between activated avß3 and angiogenesis is quite striking. In addition, our study showed that that the ability of tumour cell avß3 to enhance angiogenesis depends very much on the microenvironment,” said Senior Research Associate Mihaela Lorger, the first author of the study.
Felding-Habermann said that the receptor’s varying effects on tumour cells depending on their location in the body reinforces a principle that her lab uncovered a few years ago.
“For tumour 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 tumour cells can do within different tissues. The shape of the molecule can increase or reduce the receptor’s affinity for its natural ligands,” she said.
The new study involved mouse models, and showed that activated avß3 on tumour cells leads to angiogenesis in the brain by elevating the expression of the VEGF, a protein that is critical to the formation of new blood vessels.
Tumour cells normally try to recruit more blood vessels when oxygen supply runs low. When oxygen and nutrients get scarce, many tumour cells die and tumour growth slows down until new vessels have formed.
However, in the brain, when activated, the tumour cell receptor promotes rapid tumour growth by enabling tumour cells to attract new blood vessels continuously, even when oxygen is still abundant.
The scientists plan to follow up on their new findings by testing if activated receptor on tumour cells also supports brain metastasis of other types of cancer, and by investigating if targeting the activated form of avß3 can inhibit metastatic brain disease. (ANI)