Diverse roles of tumor-stromal PDGFB-to-PDGFRβ signaling in breast cancer growth and metastasis

Abstract

Over the last couple of decades, it has become increasingly apparent that the tumor microenvironment (TME) mediates every step of cancer progression and solid tumors are only able to metastasize with a permissive TME. This intricate interaction of cancer cells with their surrounding TME, or stroma, is becoming more understood with an ever greater knowledge of tumor-stromal signaling pairs such as platelet-derived growth factors (PDGF) and their cognate receptors. We and others have focused our research efforts on understanding how tumor-derived PDGFB activates platelet-derived growth factor receptor beta (PDGFRβ) signaling specifically in the breast cancer TME. In this chapter, we broadly discuss PDGF and PDGFR expression patterns and signaling in normal physiology and breast cancer. We then detail the expansive roles played by the PDGFB-to-PDGFRβ signaling pathway in modulating breast tumor growth and metastasis with a focus on specific cellular populations within the TME, which are responsive to tumor-derived PDGFB. Given the increasingly appreciated importance of PDGFB-to-PDGFRβ signaling in breast cancer progression, specifically in promoting metastasis, we end by discussing how therapeutic targeting of PDGFB-to-PDGFRβ signaling holds great promise for improving current breast cancer treatment strategies.

Keywords: Breast cancer; Metastasis; PDGF; PDGFR; Tumor microenvironment.