Pancreatic Stem Cell Marker and Tumor Growth Driver Identified

Pancreatic Stem Cell Marker and Tumor Growth Driver Identified

Pancreatic cancer is one of the deadliest forms of cancer. Only around 5% of patients diagnosed with this form of cancer survive more than 5 years after diagnosis.

Pancreatic cancer is particularly aggressive. It is caused by uncontrolled growth of secretory and tubular cells in the pancreas. The main problem with pancreatic cancer is it typically does not produce any symptoms until the latter stages of the disease when it is incurable.

Researchers at the Francis Crick Institute believe they have identified a potential drug target which could lead to new treatments for pancreatic cancer. The researchers studied the most common form of pancreatic cancer, pancreatic ductal adenocarcinoma, and looked at cancer stem cells – The cells which form new tumors and differentiate into several different types of tumor cells.

Through a gene expression analysis, the researchers identified a protein in the cancer stem cells, named CD9, which is present on the surface of the stem cells during the development of a tumor and also in more established tumors.

The protein could therefore be used as a marker to identify tumors, but the researchers also found that the protein is a major driver of the growth of pancreatic cancer tumor cells.  By manipulating the levels of the protein in cancer stem cells in mice, the researchers found smaller tumors were formed. When CD9 was increased, larger tumors formed and much more quickly.

Approximately 10% of patients with pancreatic ductal adenocarcinoma have high levels of CD9 and patients whose pancreatic tumors have high levels of CD9 have a much worse prognosis. While chemotherapy can be used to wipe out the tumor cells, all of those cells must be killed, or the cancer will return and CD9 will continue to fuel cancer cell growth.

An analysis of the mechanisms by which CD9 promotes cancer cell growth showed that it increases uptake of glutamine, which provides energy that allows cancer cells to grow. If treatments can be developed to target CD9, it would be possible to block uptake of glutamine and cut off the cells’ energy supply, thus starving the cancer cells.

The study is detailed in the paper – CD9 identifies pancreatic cancer stem cells and modulates glutamine metabolism to fuel tumour growth – which was recently published in the journal Nature Cell Biology. DOI: 10.1038/s41556-019-0407-1

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