Department of Pathology, School of Basic Medical Science, Wuhan University, 430071 Wuhan, China.
Int J Cancer. 2013 Jan 1;132(1):1-8. doi: 10.1002/ijc.27664. Epub 2012 Jun 26.
Macroautophagy (hereafter autophagy) is a cellular homeostatic mechanism that involves protein and organelle degradation, and has a number of connections to human physiology and diseases. Autophagy in tumor parenchyma acts as either a tumor-promoting role or a tumor-inhibiting role depending on the types and stages of tumors. In recent years, attention to autophagy in tumor stroma that is referred as "autophagic tumor stroma" has created a new paradigm to understand the role of autophagy in cancer. Here we propose that the autophagic tumor stroma is a phenomenon of adaptation at a certain stage of tumor development, and has a prominent role in tumor growth, progression and spread of tumors. This idea is supported by recent studies: (i) Autophagic tumor stroma is activated by hypoxia and cancer cells induced oxidative stress, when tumors grow to a certain stage; (ii) Autophagic tumor stroma aids in providing essential nutrients to malignant cells, remodeling the tumor microenvironment, increasing DNA damage, genetic instability and stemness in cancer cells, and decreasing the apoptotic sensitivity of cancer cells. The autophagic tumor stroma is therefore a significant determinant in tumor growth and progression and implicates an important target for cancer therapies.
自噬（下文简称自噬）是一种细胞内稳态机制，涉及蛋白质和细胞器的降解，与许多人类生理和疾病都有联系。肿瘤实质中的自噬作用根据肿瘤的类型和阶段，可能起到促进肿瘤或抑制肿瘤的作用。近年来，人们对被称为“自噬性肿瘤基质”的肿瘤基质中的自噬作用的关注，为理解自噬在癌症中的作用创造了一种新的范例。在这里，我们提出自噬性肿瘤基质是肿瘤发展的某个阶段的适应现象，在肿瘤生长、进展和肿瘤扩散中具有突出作用。这一观点得到了最近研究的支持：（i）自噬性肿瘤基质在肿瘤生长到一定阶段时，由缺氧和癌细胞诱导的氧化应激激活；（ii）自噬性肿瘤基质有助于向恶性细胞提供必要的营养物质，重塑肿瘤微环境，增加癌细胞中的 DNA 损伤、遗传不稳定性和干细胞特性，并降低癌细胞的凋亡敏感性。因此，自噬性肿瘤基质是肿瘤生长和进展的重要决定因素，暗示了癌症治疗的一个重要靶点。
