Head and neck cancer cells sequester nearby healthy tissues, promoting a new invasion of cancer cells

Up to half of patients with squamous cell carcinoma of the head and neck will experience tumor recurrences or new tumors, tumors that often spread and are difficult to treat.

A team of scientists led by the University of Michigan School of Dentistry identified a mechanism by which the head and neck cancer cells subverts adjacent normal tissue, allowing small groups of cancer cells to bury beneath healthy tissue.

The team decided to examine this specific mechanism of head and neck cancer because a specific gene, DMBT1, appeared on a screen of genes that are silenced during oral cancer, said lead researcher Nisha D’Silva, Donald A. Kerr’s associate professor of oral pathology.

Researchers at D’Silva’s lab found that when DMBT1 was suppressed in head and neck cancer cells, it promoted aggressive invasion and metastasis in laboratory studies and was associated with metastasis in patients.

They also discovered that two proteins were secreted cap and neck cancer cells suppress DMBT1 in nearby healthy tissue, subverting it to promote the invasion of a small number of cancer cells, which are buried beneath healthy tissue.

The researchers examined this mechanism in mice, chick embryos, and human cancer cell cultures. In chick embryos, none of the tumors overexpressing DMBT1 metastasized, while most control tumors that had low DMBT1 metastasized, D’Silva said.

“The importance of this paper is that the loss of DMBT1 in cancer cells and adjacent normal tissue benefits cancer cells, allowing them to travel in small groups away from the main tumor,” he said. “That’s why cancer cells require the help of adjacent tissue. Finding ways to disrupt this communication and improve DMBT1 expression could help improve outcomes.”

The findings, published in Journal of Experimental Medicine, could open up possibilities for new therapeutics that target proteins D’Silva, in cancer cells that regulate DMBT1 and may have implications for other cancers in which DMBT1 expression is altered.

“We are familiar with cancer cells that need the help of other cell types to grow and spread,” he said. “Our research showed that cancer cells also communicate with healthy cells of their own cell type to facilitate spread.”

None i neck cancer it is the sixth most common cancer in the world, with 600,000 new cases a year.