KLK3/PSA and cathepsin D activate VEGF-C and VEGF-D

Surprisingly, VEGF-C might have a function in reproductive biology. However, the connection to cancer is for us even more exciting...

After ADAMTS3, we describe two new proteases, that are able to activate VEGF-C. Kallikrein-related pepdidase 3 (KLK3, aka prostate-specific antigen PSA) cleaves VEGF-C in human ejaculate and cathepsin D might do the same with latent, extracellular matrix-associated VEGF-C, when you lick your wounds. However, there is data indicating that both KLK3 and cathepsin D are involved in the activation of VEGF-C and VEGF-D in cancer. Tumors might use VEGF-C/D and these proteases to become resistant to anti-VEGF-A therapy ("Avastin"). Thus, in our next experiments, we will try to inhibit these proteases and see whether we can prevent tumor angiogenesis and/or tumor metastasis.

The research establishing this surprising connection between the function of PSA in reproductive biology and in tumor development was published in eLIFE: https://doi.org/10.7554/eLife.44478