Head and neck squamous cell carcinomas (
HNSCC) belong among severe and highly complex malignant diseases showing a high level of heterogeneity and consequently also a variance in therapeutic response, regardless of clinical stage. Our study implies that the progression of
HNSCC may be supported by cancer-associated fibroblasts (CAFs) in the tumour microenvironment (TME) and the heterogeneity of this disease may lie in the level of cooperation between CAFs and epithelial
cancer cells, as communication between CAFs and epithelial
cancer cells seems to be a key factor for the sustained growth of the tumour mass. In this study, we investigated how CAFs derived from tumours of different
mRNA subtypes influence the proliferation of
cancer cells and their metabolic and biomechanical reprogramming. We also investigated the clinicopathological significance of the expression of these metabolism-related genes in tissue samples of
HNSCC patients to identify a possible gene signature typical for
HNSCC progression. We found that the right kind of cooperation between
cancer cells and CAFs is needed for tumour growth and progression, and only specific
mRNA subtypes can support the growth of primary
cancer cells or
metastases. Specifically, during coculture,
cancer cell colony supporting effect and effect of CAFs on cell stiffness of
cancer cells are driven by the
mRNA subtype of the tumour from which the CAFs are derived. The degree of colony-forming support is reflected in
cancer cell glycolysis levels and
lactate shuttle-related transporters.