癌相关成纤维细胞在肿瘤葡萄糖代谢中的作用

瓦博格效应认为,即便在氧气充足时,肿瘤仍大量利用葡萄糖进行有氧糖酵解,产生乳酸和少量ATP。虽产能效率低,但中间产物有利于改造肿瘤微环境,促进肿瘤恶性进展。近年发现,成纤维细胞作为肿瘤间质的重要组成部分,在肿瘤细胞诱导下具有癌相关成纤维细胞（cancer-associated fibroblast, CAF）表型,通过自身线粒体功能障碍、自噬而持续向肿瘤细胞提供生物大分子合成原料,用以促进肿瘤增殖、侵袭、转移、耐药。相反,肿瘤细胞自身则提高线粒体代谢水平,进行氧化磷酸化,此现象被命名为反瓦博格效应。CAF与酸化的微环境驱动肿瘤细胞自发选择葡萄糖代谢方式、促进肿瘤恶性进展。

The effect of cancer-associated fibroblast in glucose metabolism of tumor cells

Warburg effect described a phenomenon that tumor cells undergoing aerobic glycolysis even with enough oxygen, generating lactic acid and little ATP. Although it had a low efficiency of energy production, lactic acid and other products may work as intermediates to modify tumor microenvironment and promote tumor progression. Recently, it’s reported that fibroblasts, an important part of tumor stroma, were endowed with cancer-associated fibroblast(CAF)phenotype such as undergoing aerobic glycolysis, mitophagy and mitochondrial dysfunction. CAF provided lactic acid and other intermediates as building blocks for macromolecule anabolism, which could facilitate tumor proliferation, invasion,metastasis and drug resistance. On the contrary, tumor cells obtained activated oxidative phosphorylation and mitochondrial metabolism, which was named as "reverse Warburg effect". The two theory unveiled a metabolic flexibility and cross-talk among tumor cells and acidic tumor microenvironment, which facilitates tumor progression.