New role for Vascular Endothelial Growth Factor in regulating skin cancer stem cells

October 19, 2011

Skin squamous cell carcinomas are amongst the most frequent cancers in humans. Recent studies suggest that skin squamous cell carcinoma, like many other human cancers, contain particular cancer cells, known as cancer stem cells, that present increased self-renewal potential that sustain tumor growth. Little is known about the mechanisms that regulate cancer stem cell functions.

To dissect the mechanisms that regulate cancer , the researchers determined which genes are preferentially expressed by cancer stem cell of skin tumors. They found that VEGF, a molecule known to regulate the formation of new vessels, is expressed at high level by skin cancer stem cells, which are located in close contact to the blood vessels. Administration of an antibody that decreases new to mice presenting results in a reduction of the pool of cancer stem cells leading to a reduction of the tumor size, demonstrating that vascular cells regulates skin cancer stem .

To determine whether VEGF secretion by cancer stem cells directly regulates the function of cancer stem cells, the authors genetically removed VEGF specifically in , and found that upon VEGF ablation, skin cancer stem cells are rapidly lost due to a defect in their renewal properties, leading to tumour regression.

"It was extremely exciting to see the complete disappearance of these tumors only two weeks after the treatment" said Benjamin Beck, the first author of the Nature paper.

The authors also found that Neuropilin 1, a VEGF receptor, is also highly expressed by skin cancer stem cells, and showed that Neuropilin 1 expression by cancer stem cells is critical to promote cancer stem cell renewal and tumour growth. In addition, the authors found that Neuropilin 1 is also essential for tumour formation, demonstrating the critical role of Neuropilin 1 during both cancer initiation and tumor growth.

Altogether this new study provides novel and important insights into the mechanisms by which VEGF controls tumour growth. VEGF signalling in endothelial cells is critical to sustain the formation of the vascular niche, promoting indirectly the renewal of skin cancer stem cells. VEGF secretion by cancer stem cells acts also directly on cancer stem cells by a Neuropilin 1 dependent mechanism to promote cancer stem cell renewal and tumor growth.

"Anti-VEGF therapies are currently used to treat cancers. 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 may be more effective for the treatment of certain cancers compared to the therapeutic strategies blocking VEGF function only in endothelial cells" said Cédric Blanpain, the senior and corresponding author of the Nature paper.

In conclusion, this new study, published in the online early edition of Nature, identifies a dual role for VEGF in regulating skin cancer stem cells and tumor progression.

Explore further: Cancer stem cells recruit normal stem cells to fuel ovarian cancer

More information: Beck B et al, The vascular niche and a VEGF/Nrp1 loop regulates the initiation and stemness of skin tumours, Nature, 2011, doi:10.1038/nature10525

Related Stories

Cancer stem cells recruit normal stem cells to fuel ovarian cancer

July 18, 2011
Researchers at the University of Michigan Comprehensive Cancer Center have found that a type of normal stem cell fuels ovarian cancer by encouraging cancer stem cells to grow.

Picking cancer stem cells out of the crowd

June 15, 2011
(Medical Xpress) -- Stem cells receive a vast amount of research attention due to their abilities to differentiate, heal, and divide in perpetuity, properties that yield promise for regenerative medicine. In cancer stem cells, ...

Recommended for you

CAR-T immunotherapy may help blood cancer patients who don't respond to standard treatments

October 20, 2017
Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine in St. Louis is one of the first centers nationwide to offer a new immunotherapy that targets certain blood cancers. Newly approved ...

Researchers pinpoint causes for spike in breast cancer genetic testing

October 20, 2017
A sharp rise in the number of women seeking BRCA genetic testing to evaluate their risk of developing breast cancer was driven by multiple factors, including celebrity endorsement, according to researchers at the University ...

Study shows how nerves drive prostate cancer

October 19, 2017
In a study in today's issue of Science, researchers at Albert Einstein College of Medicine, part of Montefiore Medicine, report that certain nerves sustain prostate cancer growth by triggering a switch that causes tumor vessels ...

Gene circuit switches on inside cancer cells, triggers immune attack

October 19, 2017
Researchers at MIT have developed a synthetic gene circuit that triggers the body's immune system to attack cancers when it detects signs of the disease.

One to 10 mutations are needed to drive cancer, scientists find

October 19, 2017
For the first time, scientists have provided unbiased estimates of the number of mutations needed for cancers to develop, in a study of more than 7,500 tumours across 29 cancer types. Researchers from the Wellcome Trust Sanger ...

Researchers target undruggable cancers

October 19, 2017
A new approach to targeting key cancer-linked proteins, thought to be 'undruggable," has been discovered through an alliance between industry and academia.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.