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

Septelia Inawati Wanandi,Sri Suciati Ningsih,Hijrah Asikin,Rendy Hosea,Gladies Mercya Grameinie Neolaka

doi:10.21315/mjms2018.25.3.2

Septelia Inawati Wanandi, Sri Suciati Ningsih + Show 3 more

Open Access

https://doi.org/10.21315/mjms2018.25.3.2

Copy DOI

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.

Highlights

According to the World Health Organization (WHO), cancer is the uncontrolled growth of cells which can invade healthy tissue and spread to distant sites in the body [1]
The proteins are distinctly expressed in glycolytic and oxidative cells and could be used as functional biomarkers of symbiotic metabolism in some types of cancer such as those of the head and neck (HNSCC) [30, 32]. The functions of both proteins depend on their interaction with the chaperone protein CD147, which is required for the trafficking process and cellular localisation of MCT1 and MCT4 at the post-translational level [31]
In some types of tumours, cancer-associated fibroblasts (CAFs) switch their metabolism from oxidative phosphorylation to glycolysis