Cancer Protects Itself via Inflammatory Pathways


A few years ago, scientists in the laboratory of Stanford’s Irving Weissman, MD, discovered that cancer cells cover themselves in copies of the CD47 “don’t eat me” protein to protect themselves from being engulfed and devoured by immune cells called macrophages.

What they could never really tell though, is how the cancer cells actually increased the production of CD47.

Recently, however, Weissman and his colleagues discovered that cancer cells accomplish this trick by recruiting molecular pathways usually used for inflammatory processes. One particular pathway involves a protein called tumour necrosis factor (TNF-alpha), which is produced in response to infection or trauma. It attracts and activates macrophage cells, which destroy sick or damaged cells. Ironically, that same genetic machinery is being used by cancer cells to protect themselves from those macrophages. The research study was published in the journal Nature Communications.

Usually TNF-alpha is involved in attracting immune cells to tissues that need to be healed,” said Paola Betancur, PhD, a postdoctoral researcher in the Weissman lab and first author on the paper. “But in this case, the tumour is using the same inflammatory mechanisms to protect itself by increasing CD47 production.”

The researchers found that TNF-alpha stimulates transcription by binding to a genomic region associated with the CD47 gene known as a “super-enhancer.” Tumour cells can evolve super-enhancers by leaving more of their DNA free for multiple transcription factors to bind, resulting in a kind of critical mass that markedly increases the production of the associated protein. 

By mapping enhancers, we showed that each cancer can lock in the permanent increase in CD47 production by turning enhancers into super-enhancers,” said Weissman, who is director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine and the director of the Stanford Ludwig Center for Cancer Stem Cell Research and Medicine.

The team then tested possible anti-cancer therapies. After implanting human breast cancer samples into mice, they treated the breast tumours with antibiotics to TNF-alpha and/or to CD47, with the goal of triggering an immune attack. Since both these mechanisms can decrease the amount of CD47 “don’t eat me” signal that the macrophages see, using both antibodies together should boost the anti-cancer activity of the immune system, which is exactly what the scientists saw.

The team now plans to test if this strategy works with other kinds of cancers.

 

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About LFCT

This is a blog about CHILDHOOD CANCER and CHILDHOOD CANCER AWARENESS Little Fighters Cancer Trust is a non-profit organisation that offers support and aid to Children with Cancer and their families. When a child is diagnosed with cancer it affects the whole family. One of the parents, usually the mother, must give up their job to care for the child and this creates financial problems for the family. In South Africa especially the majority of these families are not well-to-do; many of them are rural. A diagnosis of cancer can wipe out any family’s finances, let alone a poor family. The costs of special medications, special diets, hospital stays, transport to and from the hospital or clinic and accommodation and food costs for the mother who spends most of the time at her child’s bedside are astronomical. These are the people and problems that fall through the cracks, and these are the people that Little Fighters Cancer Trust has pledged to help in any way possible. LFCT takes a holistic approach to assisting the Children with Cancer and their Families, with the main aim to be the preservation of individual dignity and pride. Little Fighters Cancer Trust also focuses on promotion and advocacy of National Childhood Cancer Awareness in an effort to increase awareness of Early Warning Signs of Childhood Cancer. This would result in earlier diagnosis, giving the Child with Cancer more of a chance at Treatment and Survival. See "About" for more Background info

Posted on 16 May, 2017, in Blog, Research and tagged , , , , , , , , , . Bookmark the permalink. Leave a comment.

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