Bone marrow mesenchymal stem cells interact with head and neck squamous cell carcinoma cells to promote cancer progression and drug resistance

Head and neck cancers are often diagnosed at later stages with poor outcomes. Mesenchymal stem cells (MSC) are recruited to primary tumor sites where they can have pro- and antitumorigenic influence. In trying to better understand the dynamics between MSC and cancer cells, we found that head and neck cancer-MSC exposure resulted in mesenchymal features, elevated proliferation rate, and were more motile, like the same cells that fused with MSC. We orthotopically grafted the parental head and neck cancer cells, those fused with MSC, or those exposed to MSC into the tongues of mice. The cancer cells originally incubated with MSC developed larger more aggressive tumors compared to the parental cell line. RNA sequencing analysis revealed the expression of genes associated with drug resistance in the cancer cells exposed to MSC compared to parental cancer cells. Strikingly, MSC exposed cancer cell lines developed paclitaxel resistance that could be maintained up to 30 d after the initial co-incubation period. The secretory profile of the MSC suggested IL-6 to be a potential mediator of epigenetic imprinting on the head and neck cancer cells. When the MSC-imprinted cancer cells were exposed to the demethylation agent, 5-aza-2'deoxycytidine, it restored the expression of the drug resistance genes to that of parental cells. This study demonstrated that the recognized recruitment of MSC to tumors could impart multiple protumorigenic properties including chemotherapy resistance like that observed in the relatively rare event of cancer/MSC cell fusion.

Automated summary

Head and neck cancers diagnosed at later stages often exhibit poor outcomes. Exposure of head and neck cancer cells to mesenchymal stem cells (MSC) led to increased tumor size, proliferation rate, and motility, as well as drug resistance. RNA sequencing analysis showed upregulation of drug resistance genes in cancer cells exposed to MSC. The secretory profile of MSC indicated IL-6 as a potential mediator of epigenetic imprinting on cancer cells.