PDGF receptors in tumor stroma: Biological effects and associations with prognosis and response to treatment

Platelet-derived growth factor (PDGF) ligands and their receptors (PDGFRα and PDGFRβ) regulate mesenchymal cells, such as fibroblasts and pericytes. These cells are important constituents of tumor stroma where they impact on tumor growth, metastasis and drug response. Studies in model systems have demonstrated ability of the PDGF system to regulate the tumor-stimulatory effects of fibroblasts, as well as their ability to promote cancer cell migration and invasion. Animal studies imply PDGFR-signaling as a regulator of tumor drug uptake. Emerging correlative analyses of different tumor collections are identifying clinically relevant variations in stromal PDGFR status, and associations between PDGFR status in tumor stroma and survival. These associations could either relate to effects of stromal PDGFR signaling on the natural course of the disease or response to treatment. The availability of clinically approved PDGFR-inhibitory drugs suggest interesting possibilities for novel clinical studies, performed on selected patient sub-groups, which further exploits tumor stroma-derived PDGFR signaling. Regulatory roles of stromal PDGF receptors. In most common cancer types PDGFRβ is expressed, at variable levels, in cancer-associated fibroblasts (starshaped cells) and perivascular cells. PDGFRα is predominantly detected in cancer-associated fibroblasts. Mechanistic studies have identified diverse effects of PDGFR signaling, or PDGFR positive cells, as summarized in the Table. Asterisk (*) indicate the existence of correlative data from analyses of clinical samples compatible with the mechanisms implied from experimental studies. [Display omitted]