Prognostic, predictive and therapeutic potential of PDGFR-positive cancer-associated fibroblasts
Session type: Symposia
Cancer-associated fibroblasts (CAFs) exert major influence on tumour growth, drug response and metastasis as recipients and providers of paracrine signals. PDGF receptors show differential expression on CAFs of most types of solid tumours, and signalling through these receptors control CAF phenotypes.
Earlier studies from our group have demonstrated that high stromal PDGF receptor expression is associated with bad prognosis in prostate cancer and invasive breast cancer. Ongoing studies are extending these findings by analyses of large series of colorectal cancer, pancreatic cancer and breast DCIS.
Ongoing studies also indicate that PDGFR-dependent paracrine signalling from fibroblasts modulate drug-sensitivity of cancer cells. More specifically, PDGF-stimulated fibroblast were found to reduce the sensitivity of breast and colorectal cancer cells to HER2- and EGFR-antibodies, through mechanism(s) involving secretion of HGF from fibroblasts.
Pro-metastatic effects of PDGF-stimulated fibroblasts are also suggested by a recent study which demonstrated that PDGF-stimulation of fibroblasts increase their ability to promote migration and invasion of co-cultured cancer cells. Experiments expanding these findings identified STC1 as a critical PDGF-induced mediator of the pro-invasive effects of fibroblast. Interestingly, STC1-/- fibroblast subsequently showed reduced ability to support metastatic growth of colorectal cancer in an orthotopic mouse model.
Collectively these studies identify PDGFR+ CAFs as important modulators of drug response and metastasis. Findings should thereby encourage to continued explorations of the clinical relevance of this cell type for prognosis, response prediction and therapy.