Some Cancers Induce Cellular Senescence to Aid in Growth – Fight Aging!


Some Cancers Induce Cellular Senescence to Aid in Growth

The presence of senescent cells can make a tissue environment more hospitable for cancer, as senescent cells secrete growth factors in addition to pro-inflammatory signals. Researchers have provided evidence for some cancers to aggressively employ the strategy of inducing senescence. Here, a research group notes that this induction of senescence can act to suppress the local immune response to a cancer by co-opting immune cells, making them senescent. It remains an open question as to whether targeting senescent cells for destruction is a good idea in the early stages of a cancer, rather than leaving them in place to attract the immune system to the tumor, but this work suggest that it will be useful, acting to remove pro-cancer signaling.

Cancerous tumors consist of a mixture of cells, the most important of which are cancer stem cells. These cells are capable of establishing new cancerous tumors by evading the immune response. Researchers examined the mechanisms by which cancer stem cells evade immune response in mice models. They showed that cancer stem cells induce senescence in macrophages – the immune cells which are responsible for the first step of the destruction of cancer cells.

The team used two cell lines of glioblastoma tumor, one of which was capable of inducing tumor formation (cancer stem cell) and the other of which was not. In mice models, the cancer stem cells suppressed the proliferation of macrophages; further investigation showed that macrophages cultured with cancer stem cells exhibit senescence or cellular aging. Macrophages were not the only immune cells affected; while the proliferation of T cells was unchanged, their antitumor activity was suppressed due to the immunosuppressive factors produced by senescent macrophages. The team identified interleukin 6 (IL-6) produced by cancer stem cells as the molecule responsible for triggering these effects.

The team also demonstrated that supplementing the mice inoculated with cancer stem cells with a molecule called nicotinamide mononucleotide resulted in the proliferation of non-senescent macrophages and reduced the immunosuppressive factors produced by senescent macrophages, preventing tumor growth and leading to increased survival times in mice. Future work will focus on two avenues: confirming that this discovery holds true for cancers other than glioblastomas, and confirming that the findings apply to cancers in humans.



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