Department of Biological Regulation, Weizmann Institute, Rehovot, Israel.
NMR Biomed. 2011 Jul;24(6):569-81. doi: 10.1002/nbm.1632. Epub 2011 Jan 17.
Tumors emerge as a result of the sequential acquisition of genetic, epigenetic and somatic alterations promoting cell proliferation and survival. The maintenance and expansion of tumor cells rely on their ability to adapt to changes in their microenvironment, together with the acquisition of the ability to remodel their surroundings. Tumor cells interact with two types of interconnected microenvironments: the metabolic cell autonomous microenvironment and the nonautonomous cellular-molecular microenvironment comprising interactions between tumor cells and the surrounding stroma. Hypoxia is a central player in cancer progression, affecting not only tumor cell autonomous functions, such as cell division and invasion, resistance to therapy and genetic instability, but also nonautonomous processes, such as angiogenesis, lymphangiogenesis and inflammation, all contributing to metastasis. Closely related microenvironmental stressors affecting cancer progression include, in addition to hypoxia, elevated interstitial pressure and oxidative stress. Noninvasive imaging offers multiple means to monitor the tumor microenvironment and its consequences, and can thus assist in the understanding of the biological basis of hypoxia and microenvironmental stress in cancer progression, and in the development of strategies to monitor therapies targeted at stress-induced tumor progression.
肿瘤的发生是遗传、表观遗传和体细胞改变的序贯获得的结果，这些改变促进了细胞增殖和存活。肿瘤细胞的维持和扩增依赖于它们适应微环境变化的能力，以及重塑周围环境的能力。肿瘤细胞与两种相互关联的微环境相互作用：代谢细胞自主微环境和非自主细胞-分子微环境，包括肿瘤细胞与周围基质之间的相互作用。缺氧是癌症进展的核心因素，不仅影响肿瘤细胞自主功能，如细胞分裂和侵袭、对治疗的抵抗和遗传不稳定性，还影响非自主过程，如血管生成、淋巴管生成和炎症，所有这些都有助于转移。除了缺氧，影响癌症进展的密切相关的微环境胁迫因素还包括间质压力升高和氧化应激。无创成像提供了多种监测肿瘤微环境及其后果的手段，因此可以帮助我们理解缺氧和微环境应激在癌症进展中的生物学基础，并开发监测针对应激诱导的肿瘤进展的治疗策略。
