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By Using iPS Cells, Okayama University Group Resolves How Cancer Cells Form Their Foundation for Multiplication

Okayama University research group found that "cancer stem cells" which generate cancer cells also produce cancer-associated fibroblasts (CAFs) which are main bodies of cancer tissues. Although CAFs are said to produce a substance which promotes growth of cancer cells and holds the key to their multiplication, it was not thought until now that they could be derived from cancer stem cells. The group used artificial pluripotent stem cells (iPS cells) in mice to verify this. The result is likely to advance research on cancer stem cells, which was mostly unknown to us. The paper on this subject has recently been published in the electronic version of a British scientific journal.

Cancer tissue consists of many cell groups related to proliferation, including blood vessel cells that surround cancer cells and supply nutrition. The type of cells most often observed is called cancer-associated fibroblasts (CAFs). They create substances which trigger the growth and spread of cancer cells as a "foundation for growth." For this reason, relationship and interaction between cancer cells and CAFs has been drawing attention, but detailed mechanism of how CAFs are formed was unknown.

Professor Masaharu Seno of Okayama University Graduate School of Natural Sciences and Lecturer Tomonari Kasai’s group said that iPS technologies were used in this research instead of conventional gene mutation. In 2012, Professor Seno and his team had already succeeded in transforming iPS cells into cancer stem cells by inducing differentiation. This time, culture fluid (culture supernatant) from human breast cancer cell line was used to induce differentiation.

The research group had carefully analyzed how cancer stem cells made from mouse iPS cells had turned into cancer cells. As a result, it was confirmed that the transformed cancer stem cells possessed properties of CAFs. It was judged that cancer stem cells were producing CAFs. Based on the first discovery in the world of this kind, the group believes that cancer stem cells are renewing themselves by differentiating into CAFs.

Cancer stem cells have the ability to renew themselves and to turn into any type of cell. They are the foundation which generates cancer cells. Due to such properties, they are less prone to react to anticancer drugs and chemotherapy. Cancer stem cells have been attracting much attention in recent research. They were difficult to discover as they only existed in very small amount within each cancer cell. For these reasons, it is expected that research on cancer stem cells will progress more in the future by Professor Seno’s method using mouse iPS cells.

Presentation by Students
Image of "cancer-related fibroblast (CAF)" born through differentiation from cancer stem cells. Scale bar on left 200 μm; scale bar on right 100 μm (Data provided by Okayama University research group)