Breast cancer is a heterogeneous disease driven not only by evolutionally diverse cancer cell themselves but also by highly dynamic microenvironment. At the center of the tumor microenvironment, tumor vasculature plays multiple roles from supporting tumor growth to providing a route for metastasis to the distant organ sites. Blood vessels in breast cancer present with perfusion defects associated with vessel dilation, tortuosity, and poor perivascular coverage (Li et al., Ultrasound Med 32:1145-1155, 2013; Eberhard et al., Cancer Res 60:1388-1393, 2000; Cooke et al., Cancer Cell 21:66-81, 2012). Such abnormal vascular system is partly due to the morphological and molecular alteration of pericytes that is accompanied by a significant heterogeneity within the populations (Kim et al., JCI Insight 1:e90733, 2016). While pericytes are implicated for their controversial roles in breast cancer metastasis (Cooke et al., Cancer Cell 21:66-81, 2012; Gerhardt and Semb, J Mol Med (Berl) 86:135-144, 2008; Keskin et al., Cell Rep 10:1066-1081, 2015; Meng et al., Future Oncol 11:169-179, 2015; Xian et al., J Clin Invest 116:642-651, 2006), the impact of their heterogeneity on breast cancer progression, metastasis, intratumoral immunity, and response to chemotherapy are largely unknown. Due to the complexity of angiogenic programs of breast cancer, the anti-angiogenic or anti-vascular treatment has been mostly unsuccessful (Tolaney et al., Proc Natl Acad Sci U S A 112:14325-14330, 2015; Mackey et al., Cancer Treat Rev 38:673-688, 2012; Sledge, J Clin Oncol 33:133-135, 2015) and requires much in-depth knowledge on different components of tumor microenvironment and how these stromal cells are interacting and communicating to each other. Therefore, understanding pericyte heterogeneity and their differential functional contribution will shed light on new potential approaches to treat breast cancer.
Keywords: Angiogenesis; Blood vessels; Breast cancer; Heterogeneity; Metastasis; PDGFRβ; Pericyte; Perivascular phenotypes; Tumor immunity; Tumor microenvironment; Vascular normalization.