Ovarian Cancer Research Symposium: Heterogeneity of Cancer-Associated Fibroblasts
Posted: Thursday, October 4, 2018
In high-grade serous ovarian cancer, cancer-associated fibroblasts may play a role in the promotion of cancer cell proliferation and invasion, as well as mediation of chemotherapy resistance. Researchers have now identified two patient subgroups based on their cancer-associated fibroblast gene signatures: one with a high expression of fibroblast activation protein (FAP-H) and one with a low expression (FAP-L). Unlike the FAP-L subtype, which is often “outcompeted” in vitro by the other phenotype, FAP-H aggressively promotes proliferation, invasion, and therapy resistance of cancer cells.
“Our discovery of [cancer-associated fibroblast] heterogeneity in [high-grade serous ovarian cancer] highlights the need to personalize patient treatment with respect to both cancer and stromal phenotypes,” stated Laurie E. Ailles, PhD, of the University Health Network, Toronto, Canada, and colleagues. Their study was presented at the 2018 Ovarian Cancer Research Symposium in Seattle, which was hosted by The Rivkin Center for Ovarian Cancer and the American Association for Cancer Research.
Dr. Ailles and her team stratified patients from The Cancer Genome Atlas (TCGA) and their own institute into the two subtypes. The FAP-H phenotype was associated with significantly shorter disease-free and overall survival in both cohorts. They also identified a transcriptional repressor, TCF21, as a transcription factor specific to FAP-L. The ability of FAP-H cancer-associated fibroblasts to promote cancer cell invasion and tumor growth was partially reversed when TCF21 was overexpressed.
“FAP-H patients may benefit from inhibition of cancer-stroma interactions or from epigenetic modulators that reprogram cancer-promoting FAP-H [cancer-associated fibroblasts] into the non-supportive FAP-L state,” concluded the investigators.
