Cancer-specific stem cell identified for gastric cancer

Scientists have identified the cancer-specific stem cell that causes gastric cancer. This discovery opens up the possibility of developing new drugs for the treatment of this disease and other types of cancers.

The research group, led by Chan Shing Leng, PhD, of the Cancer Science Institute of Singapore, Malaysia, demonstrated for the first time that a cancer-specific variant of a cell surface protein, CD44v8-10, marks gastric cancer stem cells but not normal cells. The study was also the first to be conducted with human gastric tissue specimens and took 5 years to complete. This study was published in Cancer Research (2014; doi:10.1158/0008-5472.CAN-13-2309).

Gastric cancer is a major cause of cancer-related deaths worldwide, with low survival and high recurrence rates for patients with advanced disease. New therapies for the treatment of gastric cancer are urgently needed.

Many cancer cell types express high levels of a cell surface protein known as CD44. This protein marks cancer stem cells that are thought to be responsible for resistance to current cancer therapy and tumor relapse. CD44 exists in many forms, and its standard form, CD44s, is found in high abundance on normal blood cells. It was previously not known which form of CD44 is found on cancer stem cells. This is critical as an ideal cancer target should mark cancer cells but not normal cells.

Research by the team and other scientists in the field has led to the hypothesis that the growth of gastric cancer may be driven by cancer stem cells. In this study, the researchers analyzed 53 patient tissue samples in conjunction with patient-derived xenograft models that are derived from intestinal-type gastric cancer. A total of eight cancer cell lines were used in this study, including six new cell lines that the researchers established.

The scientists discovered a cancer-specific CD44 variant, CD44v8-10, that marks gastric cancer stem cells but not normal cells. CD44v8-10 promotes cancer cell growth and it is significantly more abundant in gastric tumor sites compared to normal gastric tissue, which makes it easily detectable. The findings results suggest that CD44v8-10 is an ideal target for developing clinical therapeutics against gastric cancer stem cells.

As CD44v8-10 is cancer specific, it may also be used as a biomarker for screening and diagnosis of gastric cancer. This is significant as biomarkers for early detection of gastric cancer are currently not available, and so doctors rely on endoscopy for the screening and diagnosis of this disease.

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