Nature 478, 399–403 (2011).Doi:10.1038/nature10525.
Benjamin Beck, Gregory Driessens, Steven Goossens, Khalil Kass Youssef, Anna Kuchnio et al.
“A vascular niche and a VEGF–Nrp1 loop regulate the initiation and stemness of skin tumours”.
Identifying how cancer stem cells and tumour growth are regulated is one of the biggest challenges oncology scientists face. Researchers in Belgium, in cooperation with German colleagues, have recently shed new light on how vascular endothelial growth factor (VEGF) is instrumental in regulating skin cancer stem cells. The study, presented in the journal Nature, was funded in part by a European Research Council (ERC) Starting Grant of EUR 1.6 million under the EU’s Seventh Framework Programme (FP7) to support the CANCERSTEM (Stem cells in epithelial cancer initiation and growth’) project . The findings reveal a dual role for the molecule VEGF in the promotion of skin cancer stem cell growth and tumour progression, which may have significant implications for the prevention and treatment of various skin cancers.
Results from past studies suggested that skin squamous cell carcinomas contain specific cancer cells, so-called ‘cancer stem cells’, which show a stronger potential to self-renew and which contribute to tumour growth. However, information about the precise mechanisms that regulate cancer stem cell functions has been lacking … until now.
Scientists led by the Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM) at the Université libre de Bruxelles in Belgium have discovered a new connection between skin cancer stem cells growth and VEGF.
Dr Benjamin Beck at IRIBHM and his colleagues discovered that VEGF, a molecule that normally promotes new blood vessel formation, is expressed at high levels by skin cancer stem cells. The team genetically removed the expression of VEGF by tumour cells, and discovered that skin cancer stem cells were quickly lost due to a defect in their renewable properties. This in turn triggered tumour regression.
Dr. Beck, lead author of the study, says: ‘It was extremely exciting to see the complete disappearance of these tumours only two weeks after the treatment.’
The receptor which binds VEGF, called Neuropilin-1, is also highly expressed by skin cancer stem cells, and is also required to promote cancer stem cell renewal and tumour growth, according to the researchers. They discovered that the Neuropilin-1 receptor plays a critical role during both cancer initiation and tumour growth.
The team says that while VEGF signalling in endothelial cells is needed indirectly by tumours to maintain the tumour’s blood supply, its production and signaling in cancer stem cells also directly promotes cancer stem cell renewal and tumour growth.
‘Anti-VEGF therapies are currently used to treat cancers,’ explains Dr Cédric Blanpain of IRIBHM, the senior author of the study. ‘These new results have important implications for the prevention and treatment of different epithelial cancers, as new therapies blocking VEGF and/or Neuropilin 1 functions in cancer cells may be more effective for the treatment of certain cancers compared to the therapeutic strategies blocking VEGF function only in endothelial cells.’