Indian Scientists, Jamia alumnus discover the role of CCN1 gene in Pancreatic Cancer Development

Indian Scientists, Jamia alumnus discover the role of CCN1 gene in Pancreatic Cancer Development

The findings of a study on a special protein in pancreatic cancer progression, known to be an angiogenic factor called CCN, co-authored by an alumnus of Jamia Millia Islmia have been published in prestigious The Scientific Reports (Nature publishing group) in May 2014.

Pancreatic cancer is an exceptionally aggressive disease, which is not easily detectable and the five year survival rate for patients is less than 5%. It represents the fourth leading cause of cancer-related deaths in the United States. Although pancreatic cancer is less common in India compared to western countries but now incidences of pancreatic cancer are increasing day by day. The disease affects one in 100,000 Indians.

A former student of the Department of Biosciences of the New Delhi’s Jamia Millia Islamia (from 1991 to 2005), Dr. Inamul Haque, a co-author and an assistant professor at the University of Kansas Medical Center told Twocircle.net through email that the aim of the study was to uncover the role of CCN1 during the communication of pancreatic cancer cells and endothelial cells in induction of tumor angiogenesis/aberrant neovascularization.

CCN1, is a matricellular protein of CCN-family, plays a vital role in pancreatic cancer progression and metastasis. Dr. Haque’s earlier findings published in the Journal of Biological Chemistry in 2013 concluded that CCN1 impacts both sonic hedgehog (SHh) and Notch pathways through integrins in pancreatic cancer cells. Both SHh and Notch signalling influence pancreatic tumor growth and contribute in the formation of tumor angiogenesis (blood vessel formation) in pancreatic cancer and other solid cancers.

“During embryonic development, CCN1 acts as an angiogenic factor, and pro-angiogenic activities of CCN1 are mediated through integrins in human umbilical vein endothelial cells which form the inner lining of blood vessels. In pancreatic cancer, the tumor cells secrete CCN1 which contributes in angiogenesis,” said Dr. Haque.

“Tumor blood vessels are different than regular blood vessels. Tumor vessels are sluggish and leaky, so when we try and treat cancer with drugs they can’t easily reach the tumor because the vessels aren’t strong,” said Drs. Sushanta Banerjee and Snigdha Banerjee, professors from the University of Kansas Medical Center and principal investigators of the study.

However, the role of CCN1 in aberrant blood vessel formation in pancreatic cancer remains unclear.

The lead author of the study, Dr. Gargi Maity, a post-doctoral fellow said: “Our combined data from different in vitro and in vivo experimental approaches displayed that pancreatic cancer cell-secreted-CCN1 promotes endothelial cell migration and aberrant capillary formation. We find that tumor angiogenic response of CCN1 was strongly dependent upon the tumor microenvironment.”

Understanding this process can lead to better targeted therapies for pancreatic cancer. When the researchers knocked down the CCN1 protein using shRNA, very few vessels and capillaries formed under mouse skin. This finding suggests that finding or creating a drug that silences CCN1 could slow down or even stop pancreatic cancer tumors from growing. “The next step would be to find an existing drug that can target the CCN1 protein, or create one,” said Dr. Snigdha.

"Our studies demonstrate that CCN1 of pancreatic cancer cells is vital for the regulation of tumor angiogenesis and thus could be an ideal target for tumor vascular disruption in pancreatic cancer,” the Banerjees concluded.