Yuen Angela, Díaz Begoña
Tumor Microenvironment and Metastasis Program, Cancer Center, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA.
Hypoxia (Auckl). 2014 Jul 16;2:91-106. doi: 10.2147/HP.S52636. eCollection 2014.
Intratumoral hypoxia is a common feature of solid tumors. Recent advances in cancer biology indicate that hypoxia is not only a consequence of unrestrained tumor growth, but also plays an active role in promoting tumor progression, malignancy, and resistance to therapy. Hypoxia signaling is mediated by the hypoxia-inducible factors (HIFs), which are not only stabilized under hypoxia, but also by activated oncogenes or inactivated tumor suppressors under normoxia. Hypoxia is a prominent feature of the tumor microenvironment of pancreatic tumors, also characterized by the presence of a fibrotic reaction that promotes, and is also modulated by, hypoxia. As the mechanisms by which hypoxia signaling impacts invasion and metastasis in pancreatic cancer are being elucidated, hypoxia is emerging as a key determinant of pancreatic cancer malignancy as well as an important target for therapy. Herein we present an overview of recent advances in the understanding of the impact that hypoxia has in pancreatic cancer invasion and metastasis.
肿瘤内缺氧是实体瘤的一个常见特征。癌症生物学的最新进展表明，缺氧不仅是肿瘤无节制生长的结果，而且在促进肿瘤进展、恶性程度及治疗抵抗方面发挥着积极作用。缺氧信号由缺氧诱导因子（HIFs）介导，HIFs不仅在缺氧状态下稳定，在常氧状态下也可被激活的癌基因或失活的肿瘤抑制因子所稳定。缺氧是胰腺肿瘤微环境的一个显著特征，其特点还包括存在促进缺氧且受缺氧调节的纤维化反应。随着缺氧信号影响胰腺癌侵袭和转移机制的逐步阐明，缺氧正成为胰腺癌恶性程度的关键决定因素以及重要的治疗靶点。在此，我们概述了对缺氧在胰腺癌侵袭和转移方面影响的最新认识进展。
