What is it about?

The research describes two new proteolytic enzymes (proteases) which are able to activate the growth factors VEGF-C and VEGF-D. While VEGF-C is necessary during the development of the lymphatic system, both VEGF-C and VEGF-D can also promote the growth and the spead of cancer (metastasis). One of the enzymes is the prostate-specific antigen (PSA), which is widely and controversially used as a marker for prostate cancer. The major physiological function of PSA is to liquefy the male ejaculate in order for sperm cells to be able to swim. Interestingly, VEGF-C and PSA occur in semen, where they may have impact on fertility. The other enzyme that is able to activate VEGF-C and VEGF-D is cathepsin D. It was already previously known that cathepsin D is related to the formation of metastases, but detailed information on the mechanism of action has been lacking.

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Why is it important?

These discoveries may help in both developing novel cancer drugs as well as identifying and treating mechanisms related to infertility.

Perspectives

This research confirms, that VEGF-C is a much more complicated growth factor that previously thought. Because of the activation by different proteases, there are many forms of active VEGF-C. Most antibodies (including those in clinical trials) do not neutralize them all (and therefore these trials are imho likely to fail). This is not evidence for a wrong concept, but just for a failing technical implementation.

Dr Michael Jeltsch
Helsingin Yliopisto

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This page is a summary of: KLK3/PSA and cathepsin D activate VEGF-C and VEGF-D, eLife, May 2019, eLife, DOI: 10.7554/elife.44478.
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