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Review
. 2018 May;25(3):7-16.
doi: 10.21315/mjms2018.25.3.2. Epub 2018 Jun 28.

Metabolic Interplay between Tumour Cells and Cancer-Associated Fibroblasts (CAFs) under Hypoxia versus Normoxia

Septelia Inawati Wanandi  1 , Sri Suciati Ningsih  2 , Hijrah Asikin  2 , Rendy Hosea  2 , Gladies Mercya Grameinie Neolaka  2
Affiliations
Review

Metabolic Interplay between Tumour Cells and Cancer-Associated Fibroblasts (CAFs) under Hypoxia versus Normoxia

Septelia Inawati Wanandi et al. Malays J Med Sci. 2018 May.

Abstract

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.

Keywords: Warburg effect; cancer-associated fibroblasts; hypoxia; lactate dehydrogenases; monocarboxylate transporters; reverse Warburg effect.

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Figures

Figure 1
Figure 1
Schematic representation of the differences between oxidative phosphorylation. A. Anaerobic glycolysis in normal cells. B. Anaerobic glycolysis in tumour cells (Warburg effect)
Figure 2
Figure 2
Metabolic interplay between glycolytic tumour cells and oxidative CAFs in hypoxia (Warburg effect)
Figure 3
Figure 3
Metabolic interplay between oxidative tumour cells and glycolytic CAFs in normoxia (Reverse Warburg effect)
See this image and copyright information in PMC

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