A new hydrogel developed by researchers at Hokkaido University and Japan’s National Cancer Center Research Institute can rapidly reprogram cancer cells into cancer stem cells, according to a study published in the journal in the journal Nature Biomedical Engineering. The double network (DN) gel could help the process of developing targeted cancer therapies.
More than 8.6 million people die annually from cancer worldwide. Despite progress with treatments, the five-year survival rate of patients with advanced-stage cancer remains low. One reason is that cancer tissues contain stem cells that are resistant to chemo- and radiotherapies. These cells can hide within tumours or circulate in the body, causing cancer recurrence.
“Cancer stem cells are a major target for anti-cancer drugs, but they are difficult to identify because they are present in very small numbers in cancer tissues,” explains Hokkaido University cancer pathologist Shinya Tanaka. “Understanding the molecular mechanisms of cancer stem cells is crucial for developing better cancer treatments.”
Cancer stem cells require a very specific microenvironment. In this study, the research team investigated whether their DN gel could recreate the right conditions to reprogram cancer cells into stem cells. The DN gel consists of a network of two chemicals and incorporates a high volume of water, making it soft and wet like biological tissues.
The DN gel successfully reprogrammed six different human cancer cell lines into stem cells in just 24 hours. When the cancer cells were placed on the DN gel, they started to form spherical structures and produce specific molecules known to be markers of cancer stem cells, suggesting they had been reprogrammed.
The researchers also uncovered some of the molecular mechanisms involved in cancer cell reprogramming. They found that calcium channel receptors and the protein osteopontin were essential for inducing tumour cells to revert into stem cells. They also found that human brain cancer cells cultured on the DN gel produced platelet-derived growth factor receptors. Adding a molecular inhibitor of these receptors allowed the scientists to target and eradicate the cancer stem cells. Also, the brain cancer cells cultured on DN gel efficiently formed tumours when transplanted into mice brains.
The team says their DN gel could help pave the way for identifying new cancer stem cell markers and developing targeted therapies.