The fight against melanoma is difficult. The rates are rising dramatically among young people, it is deadly if not caught early and the disease tends to adapt to even the most modern treatment. University of Rochester researchers made an important discovery, which can be next step to new treatment in the future.


Melanoma is one of the most malignant human . The rates and mortality are rising dramatically. UV light from the sun is the most important risk factor of disease. Melanoma is the most common form of cancer among young adults 25 to 29 and the second most common among teens and early 20s. Early diagnose is linked to 99% survival rate. The survival rate falls to 15% for people with advanced disease. One of the challenges is relapse. The neoplasm can recur and act more aggressively than the initial diagnosis. It can adapt to even the most modern treatment such as VEGF inhibitors.

The researchers from University of Rochester investigated progression of melanoma and its drug resistance to VEGF inhibitors.

VEGF – vascular endothelial growth factor is signal protein, which plays key role in angiogenesis. The angiogenesis is formation of new bood vessels to fuel the cancer. Melanoma cells release VEGF to maintain delivery of oxygen and nutrients. The Food and Drug Administration (FDA) in recent years has approved several promising cancer drugs, called antiangiogenesis therapies or VEGF inhibitors, which block the activity of VEGF protein, once it has been secreted or released by the tumor cells. Despite continuous pharmacotherapy with these antiangiogenic drugs, some VEGF escapes, creating an environment for a relapse.

The scientists from University of Rochester proposed that a receptor called GPR56, which mostly has been studied in the context of brain formation has important role in cancer progression. GPR56 can relate to the growth and spread of melanoma and might even be responsible for angiogenesis. The team wondered if VEGF could be blocked earlier, before it was produced. Knowing that some involvement with cancer cells had been reported in the literature, they began a detailed investigation of G protein couple proteins (GPCRs). In the context of other diseases GPCRs constitute 40% of drug targets, making it attractive option of control cancer progression if a link could be established.

The team used mouse model and four different human melanoma cell lines. They find GPR56 inhibits VEGF production and impedes melanoma angiogenesis and growth. Interestingly, GPR56 has two different fragments – GPRN and GPRC. They play distinct roles in regulating VEGF production and melanoma progression. Additionally, the expression levels of GPR56 were inversely correlated with the malignancy of melanomas in human subjects.

The results has been published in Cancer Research. The researchers hope their work is important for better understanding of angiogenesis and its implications. It can help to develop new therapies and antiangiogenic drugs in treatment of melanoma.

>Author : Piotr Łażewski – Banaszak

Source:
1. L. Yang, G. Chen, S. Mohanty, G. Scott, F. Fazal, A. Rahman, S. Begum, R. Hynes, L. Xu. GPR56 Regulates VEGF Production and Angiogenesis during Melanoma Progression. Cancer Research, 2011; DOI: 10.1158/0008-5472.CAN-10-4543
2. University of Rochester Medical Center (2011, July 21). Exploring keys to melanoma progression. ScienceDaily. Retrieved July 28, 2011, from http://www.sciencedaily.com/releases/2011/07/110720142513.htm