Scientists Explain How Metastatic Lesions Thrive In The Brain

In what may become a new drug target for metastatic brain cancer, scientists from have discovered a molecular mechanism that plays a pivotal role in controlling cancer growth in the brain.

The discovery is made by scientists from The Scripps Research Institute.

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"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 tumur cells that have invaded the brain, a tumur cell receptor known as integrin avï¿½3 increased the supply of a growth factor involved in the development of new blood vessels ("angiogenesis") necessary for tumur expansion within the brain tissue.

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In contrast, the same receptor did not influence tumor growth at the primary cancer site, in this case, the breast.

"The fact that we uncovered a link between activated avï¿½3 and angiogenesis is quite striking. In addition, our study showed that that the ability of tumor cell avï¿½3 to enhance angiogenesis depends very much on the microenvironment," said Senior Research Associate Mihaela Lorger, the first author of the study.

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Felding-Habermann said that the receptor's varying effects on tumor cells depending on their location in the body reinforces a principle that her lab 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. 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 avï¿½3 on tumor 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.

Tumor cells normally try to recruit more blood vessels when oxygen supply runs low. When oxygen and nutrients get scarce, many tumor cells die and tumor growth slows down until new vessels have formed.

However, in the brain, when activated, the tumor cell receptor promotes rapid tumor growth by enabling tumor 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 tumor cells also supports brain metastasis of other types of cancer, and by investigating if targeting the activated form of avï¿½3 can inhibit metastatic brain disease.

Source-ANI
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