Wanandi Septelia Inawati, Ningsih Sri Suciati, Asikin Hijrah, Hosea Rendy, Neolaka Gladies Mercya Grameinie
Department of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Indonesia, Jalan Salemba Raya No. 6, Jakarta 10430, Indonesia.
Master Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jalan Salemba Raya No. 4, Jakarta 10430, Indonesia.
Malays J Med Sci. 2018 May;25(3):7-16. doi: 10.21315/mjms2018.25.3.2. Epub 2018 Jun 28.
The growth of tumour cells is closely related to cancer-associated fibroblasts (CAFs) present within their microenvironment. CAFs, the most abundant cells in tumour stroma, secrete growth factors that play pivotal roles in tumour cell proliferation, metabolism, angiogenesis and metastasis. Tumour cells adapt to rapid environmental changes from normoxia to hypoxia through metabolic interplay with CAFs. In this mini review, we discuss the role of lactate dehydrogenases (LDHs) and monocarboxylate transporters (MCTs) on the metabolic interplay between tumour cells and CAFs under hypoxia compared to normoxia. The LDHs catalyse the interchange of lactate and pyruvate, whereas MCTs facilitate the influx and efflux of monocarboxylates, especially lactate and pyruvate. To sum up, tumour cells switch their metabolic state between glycolysis and oxidative phosphorylation through metabolic interplay with CAFs, which exhibit the Warburg effect under hypoxia and reverse Warburg effect under normoxia.
肿瘤细胞的生长与其微环境中存在的癌症相关成纤维细胞（CAFs）密切相关。CAFs是肿瘤基质中最丰富的细胞，分泌在肿瘤细胞增殖、代谢、血管生成和转移中起关键作用的生长因子。肿瘤细胞通过与CAFs的代谢相互作用适应从常氧到缺氧的快速环境变化。在本综述中，我们讨论了与常氧相比，乳酸脱氢酶（LDHs）和单羧酸转运体（MCTs）在缺氧条件下肿瘤细胞与CAFs代谢相互作用中的作用。LDHs催化乳酸和丙酮酸的互换，而MCTs促进单羧酸的流入和流出，尤其是乳酸和丙酮酸。总之，肿瘤细胞通过与CAFs的代谢相互作用在糖酵解和氧化磷酸化之间切换其代谢状态，CAFs在缺氧条件下表现出瓦伯格效应，在常氧条件下表现出逆瓦伯格效应。
