Hypoxia is a common feature in tumors, driving pathways that promote epithelial-to-mesenchymal transition, invasion, and metastasis. Clinically, high levels of hypoxia-inducible factor (HIF) expression and stabilization at the primary site in many cancer types is associated with poor patient outcomes. Experimental evidence suggests that HIF signaling in the primary tumor promotes their dissemination to the bone, as well as the release of factors such as LOX that act distantly on the bone to stimulate osteolysis and form a pre-metastatic niche. Additionally, the bone itself is a generally hypoxic organ, fueling the activation of HIF signaling in bone resident cells, promoting tumor cell homing to the bone as well as osteoclastogenesis. The hypoxic microenvironment of the bone also stimulates the vicious cycle of tumor-induced bone destruction, further fueling tumor cell growth and osteolysis. Furthermore, hypoxia appears to regulate key tumor dormancy factors. Thus, hypoxia acts both on the tumor cells as well as the metastatic site itself to promote tumor cell metastasis.

缺氧是肿瘤的一个常见特征，驱动促进上皮间质转化、侵袭和转移的途径。临床上，许多癌症类型的原发部位高水平缺氧诱导因子（HIF）表达和稳定与患者预后不良相关。实验证据表明，原发肿瘤中的 HIF 信号传导促进其向骨骼的扩散，以及 LOX 等因子的释放，这些因子远程作用于骨骼，刺激骨质溶解并形成转移前的生态位。此外，骨骼本身是一个缺氧器官，促进骨驻留细胞中 HIF 信号的激活，促进肿瘤细胞归巢到骨骼以及破骨细胞生成。骨骼的缺氧微环境还会刺激肿瘤引起的骨质破坏的恶性循环，进一步促进肿瘤细胞的生长和骨质溶解。此外，缺氧似乎可以调节关键的肿瘤休眠因素。因此，缺氧既作用于肿瘤细胞，也作用于转移部位本身，促进肿瘤细胞转移。