Research led by North Carolina State University has found that when enteric glial cells are exposed to secretions from colon tumours, the glial cells convert into promoters of tumour growth.

The work demonstrates enteric glial cells' importance in the tumour microenvironment and could lead to new targets for treatment of colon cancer.

The research is published in the journal EBioMedicine.

The enteric nervous system functions as the gut's "brain," or local nervous system.

Neurones and enteric glial cells (EGCs) in the enteric nervous system work together to regulate important intestinal functions like peristalsis and help control the function of the epithelium, or intestinal lining.

When a cancerous tumour grows within the intestine, it creates a tumour microenvironment composed of resident or recruited cells such as the surrounding ECGs, neurones, blood vessels, immune cells, and various signalling molecules.

The tumour and the surrounding microenvironment interact constantly.

"Only a fraction of cancer cells - known as colon cancer stem cells, or CSCs - is thought to be able to create tumours," says Laurianne Van Landeghem, assistant professor of neurogastroenterology at NC State and corresponding author of a paper describing the work. "CSCs are constantly exposed to regulatory cues in the form of molecules secreted by neighbouring cells in the tumour microenvironment. EGCs are an important part of the tumour microenvironment, but no one had studied whether these cells affect the CSCs' ability to create new tumours."

Van Landeghem and an international team of researchers that included Ph.D. student Simon Valès from the University of Nantes, France, looked at tumours from colon cancer patients in both the U.S. and France.

"We isolated CSCs from the tumours and grew them in presence or absence of glial cells to see if the EGCs' secretions affected tumour initiation and growth," Van Landeghem says.

When the team exposed CSCs to secretions of EGCs that were grown alone and independently from the tumour, there wasn't a discernable increase in tumour growth.

However, when the team grew EGCs in the same medium in which they had grown tumour cells and then exposed those secretions to CSCs, tumours formed more quickly and were bigger.

"In the tumour microenvironment, the cancer cells secrete a molecule known as IL-1, which, if taken up by nearby EGCs, can change them," Van Landeghem says.

"Those changed glia in turn secrete a molecule known as PGE2, which stimulates the CSCs and causes tumour initiation and faster tumour growth. Both of these molecules are well described, but we didn't know they were involved in the communication between the tumour and glial cells until now.

"The tumour is essentially remodelling the nearby glia with the aim of making itself thrive. We have identified the molecules responsible for this remodelling and EGCs' pro-tumour initiation impact. Hopefully this work can lead to better understanding of the role EGCs play in colon cancer and perhaps help us identify new targets for cancer therapies."

Source: North Carolina State University