Obeagu Emmanuel Ifeanyi
Department of Biomedical and Laboratory Science, Africa University, Zimbabwe.
Ann Med Surg (Lond). 2025 May 20;87(7):4246-4254. doi: 10.1097/MS9.0000000000003411. eCollection 2025 Jul.
Breast cancer remains a significant global health challenge, with hypoxia playing a crucial role in its progression. Hypoxia, defined as reduced oxygen availability, is a hallmark of solid tumors and particularly influences the tumor microenvironment in breast cancer. Under hypoxic conditions, tumors activate a variety of molecular responses that promote survival, including the stabilization of hypoxia-inducible factors (HIFs). These transcription factors regulate the expression of pro-angiogenic genes, such as vascular endothelial growth factor (VEGF), which drive angiogenesis and support tumor growth. However, the vasculature formed under hypoxic conditions is often dysfunctional, contributing to tumor progression, metastasis, and resistance to therapies. This review explores the mechanisms by which hypoxia drives angiogenesis in breast cancer, emphasizing the roles of HIFs, VEGF signaling, and metabolic reprogramming. Angiogenesis, a critical process for tumor survival and growth, is primarily mediated by the induction of VEGF under hypoxic conditions. VEGF acts on endothelial cells to promote blood vessel formation, ensuring the tumor receives sufficient oxygen and nutrients. However, the vessels formed are typically leaky and inefficient, exacerbating the hypoxic environment and perpetuating a cycle of tumor progression. The metabolic reprogramming that occurs in hypoxic tumor cells, such as the shift toward glycolysis (the Warburg effect), also plays a pivotal role in sustaining angiogenesis. The resulting acidic conditions further enhance VEGF production and endothelial cell migration, supporting continued tumor growth and metastasis.
乳腺癌仍然是一项重大的全球健康挑战，缺氧在其进展过程中起着关键作用。缺氧被定义为氧气供应减少，是实体瘤的一个标志，对乳腺癌的肿瘤微环境有特别影响。在缺氧条件下，肿瘤会激活多种促进生存的分子反应，包括缺氧诱导因子（HIFs）的稳定。这些转录因子调节促血管生成基因的表达，如血管内皮生长因子（VEGF），后者驱动血管生成并支持肿瘤生长。然而，在缺氧条件下形成的脉管系统往往功能失调，促进肿瘤进展、转移和对治疗的抵抗。本综述探讨了缺氧驱动乳腺癌血管生成的机制，强调了HIFs、VEGF信号传导和代谢重编程的作用。血管生成是肿瘤生存和生长的关键过程，主要由缺氧条件下VEGF的诱导介导。VEGF作用于内皮细胞以促进血管形成，确保肿瘤获得足够的氧气和营养。然而，形成的血管通常渗漏且效率低下，加剧了缺氧环境并使肿瘤进展循环持续。缺氧肿瘤细胞中发生的代谢重编程，如向糖酵解（瓦伯格效应）的转变，在维持血管生成方面也起着关键作用。由此产生的酸性条件进一步增强VEGF的产生和内皮细胞迁移，支持肿瘤持续生长和转移。
