BBB Seminar: Arne Östman
The molecular basis of the effects of cancer-associated fibroblasts on tumor progression and response to therapy
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
Accumulating evidence emphasizes the roles of the tumor microenvironment for tumor biology. The cancer-associated fibroblast (CAF) is a major cell type of the tumor stroma. Different types of marker studies indicate the existence of different CAF-subsets. Recent studies have linked CAF-derived molecules to tumor progression and drug response. Clinical studies aiming at CAF-targeting are envisioned based on experimental findings with agents targeting e.g. FAP-, PDGF-, TGF-β- or hedgehog-signaling.
Recent studies in our own group have demonstrated prognostic significance of stromal PDGF receptors in breast and prostate cancer based on tissue microarray (TMA) analyses of a large series of tumors. Analyses of clinical material also indicate that stromal PDGF-receptor expression determines response to tamoxifen. Associated tissue culture studies have provided independent support for the impact of PDGF-dependent fibroblast-derived paracrine signaling on drug sensitivity of co-cultured cancer cells. Molecular identification of these PDGF-induced paracrine-signaling molecules is ongoing. Through analyses of the in situ expression profile of prostate cancer fibroblasts novel pro-tumoral CAF-derived proteins, including CXCL14, have been identified. Finally, studies on lung cancer CAFs have identified the transcription factor FoxF1 as a clinically relevant inducer of tumor-stimulating CAF phenotypes.
Host: Donald Gullberg, Department of Biomedicine