TUMOUR-MEDIATED SIGNALLING TARGETING ADIPOCYTE TRANSFORMATION INTO CANCER-ASSOCIATED ADIPOCYTES IN OBESITY
MetadataShow full item record
Adipose tissue is suggested to affect tumourigenesis and cancer progression. A special type of peritumoural adipocytes, the cancer-associated adipocytes (CAAs), may drive this cancer progression. However, the mechanisms underlying the tumour-mediated development of these CAAs remains largely unknown. Therefore, this study aims to provide an overview of the current state of knowledge, using Pubmed as database, regarding the mechanisms driving CAA development in obesity. CAAs are very heterogenic, and heterogeneity may be explained by several theories, including the heterogenetic nature of resident adipocytes, the distance of the adipocytes relative to the tumour, the differences in adipocyte precursor pools, and the transdifferentiation of peritumoural cell types. CAAs have previously been proposed to be in metabolic symbiosis with cancer cells, however, here we propose that cancer cells act as metabolic parasites on CAAs, resulting in the metabolic depletion of CAAs and trans-differentiation into cancer-associated fibroblasts (CAFs). Furthermore, adipocyte differentiation and dedifferentiation mechanisms are highlighted, as a paradox seems to exist in which both seem to occur in fat tissue in cancer. The simultaneous differentiation and dedifferentiation process can be explained by spatial differences to the tumour core and the biphasic epigenetic regulation observed in adipocyte development, yet further studies are needed to confirm this. As for the tumour-mediated signalling mechanisms, EVs, including exosomes, seem to play a pivotal role in crosstalk and metabolic symbiosis between cancer cells and adipocytes. Furthermore, an important role for exomiR-155 is laid-out, regarding its role in activating both adipocytes and fibroblasts, promote adipocyte-browning and induce catabolism to promote cancer metastasis (96). Furthermore, specific miRNAs are associated with pro-tumorigenic processes, these miRNAs include miRNA-155, miRNA-126 and miRNA-144. Lastly, obesity worsens the TME by increasing inflammation and hypoxia, stimulating both hypoxia- and inflammation-induced adipocyte differentiation and tumour progression.