Deciphering the Role of Tumor-Associated Macrophages (TAMs) in Tumor Angiogenesis

Breast cancer (BC) is among the top three cancers in the world. Age, hormonal imbalances, unhealthy lifestyles, family history, and genetic abnormalities are all significant risk factors for cancer development. Angiogenesis is a crucial step in this multifactorial process and involves various proangiogenic factors, such as VEGF, PDGF, HGF, MMPs, Angs, FGF, and TGF-β. In addition to angiogenic factors, stromal cells such as cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), and cancer stem cells (CSCs) secrete secretory factors that aid endothelial cells (ECs) in the use of angiogenic factors, resulting in tumor vascularization. Hypoxia-responsive genes, such as osteopontin (OPN), regulate HIF1α-mediated VEGF production, promoting tumor development and angiogenesis. Despite significant breakthroughs in BC therapeutics, preventing disease recurrence and chemoresistance remains a challenge in treatment regimens. Several antiangiogenic medications, including bevacizumab and ramucirumab, are employed depending on the stage of the disease. Despite significant breakthroughs in BC therapeutics, no successful breakthrough treatment has been identified for preventing the metastasis and recurrence of this disease. This review focuses on understanding the mechanism of tumor angiogenesis and the role of TAMs in fostering angiogenesis.