Instituto de Investigación Sanitaria Hospital La Fe, Valencia, Spain.
Department of Chemical Enginering, Facultad de Ingeniería y Ciencias, Universidad de La Frontera, Temuco, Chile.
Mol Biol Rep. 2022 Jul;49(7):6741-6751. doi: 10.1007/s11033-022-07299-z. Epub 2022 Mar 11.
Cancer stem cells (CSCs) are a small subpopulation of immature cells located in the tumor mass. These cells are responsible for tumor development, proliferation, resistance and spreading. CSCs are characterized by three unique features: the ability to self-renew, differentiation and tumor formation. CSCs are similar to stem cells, but they differ in the malignant phenotype. CSCs become immortal and survive harsh environmental conditions such as hypoxia, starvation and oxidative stress. However, this harsh tumor microenvironment induces the activation of autophagy, which further increases the CSCs stemness profile, and all these features further increase tumorigenicity and metastasis capacity. Autophagy is induced by the extracellular and cellular microenvironment. Hypoxia is one of the most common factors that highly increases the activity of autophagy in CSCs. Therefore, hypoxia-induced autophagy and CSCs proliferation should be elucidated in order to find a novel cure to defeat cancer cells (CSCs and non-CSCs). The remaining challenges to close the gap between the laboratory bench and the development of therapies, to use autophagy against CSCs in patients, could be addressed by adopting a 3D platform to better-mimic the natural environment in which these cells reside. Ultimately allowing to obtain the blueprints for bioprocess scaling up and to develop the production pipeline for safe and cost-effective autophagy-based novel biologics.
癌症干细胞（CSCs）是位于肿瘤团块中的一小部分不成熟细胞。这些细胞负责肿瘤的发展、增殖、耐药性和扩散。CSCs 具有三个独特的特征：自我更新、分化和肿瘤形成的能力。CSCs 类似于干细胞，但它们在恶性表型上有所不同。CSCs 变得永生，并能在缺氧、饥饿和氧化应激等恶劣环境条件下存活。然而，这种恶劣的肿瘤微环境会诱导自噬的激活，这进一步增加了 CSCs 的干性特征，所有这些特征进一步增加了肿瘤形成能力和转移能力。自噬是由细胞外和细胞微环境诱导的。缺氧是高度增加 CSCs 中自噬活性的最常见因素之一。因此，为了寻找新的治疗方法来战胜癌细胞（CSCs 和非 CSCs），应该阐明缺氧诱导的自噬和 CSCs 增殖。为了在患者中使用自噬来对抗 CSCs，可以采用 3D 平台来更好地模拟这些细胞所在的自然环境，从而解决将实验室研究转化为治疗方法方面的剩余挑战。最终，可以获得生物工艺放大的蓝图，并开发安全且具有成本效益的基于自噬的新型生物制剂的生产管道。
