Role of tissue microenvironment resident adipocytes in colon cancer

Abstract

Colorectal cancer (CRC) is a multifactorial disease characterized by several genetic and epigenetic alterations occurring in epithelial cells. It is increasingly recognized that tumour progression is also regulated by tumour microenvironment (TME). The bidirectional cross-talk between tumour resident adipocytes and cancer cells within TME has been proposed as active contributor to carcinogenesis. Tumour resident adipocytes exhibit an activated phenotype characterized by increased secretion of pro-tumorigenic factors (angiogenic/inflammatory/immune) which contribute to cancer cell proliferation, invasion, neoangiogenesis, evasion of immune surveillance and therapy resistance. Furthermore, adipocytes represent a fuel rich source for increasing energy demand of rapidly proliferating tumour cells. Interestingly, a relationship between obesity and molecular variants in CRC has recently been identified. Whether adipose tissue promotes cancer progression in subsets of molecular phenotypes or whether local tissue adipocytes are involved in inactivation of tumour suppressor genes and/or activation of oncogenes still needs to be explored. This editorial highlights the major findings related to cross-talk between adipocytes and colon cancer cells and how local paracrine interactions may promote cancer progression. Furthermore, we provide future strategies in studying colonic TME which could provide insights in bidirectional cross-talk mechanisms between adipocytes and colonic epithelial cells. This could enable to decipher critical signalling pathways of both early colonic carcinogenesis and cancer progression.

Keywords: Tumour resident adipocytes, Dysfunctional adipocytes, Adipose tissue, Cancer cell-tumour resident adipocyte cross-talk, Colon cancer microenvironment

Core tip: The tumor microenvironment (TME) has been implicated in cancer progression and chemoresistance. Adipocytes are active components of the TME. Bidirectional cross-talk between adipocytes and cancer cells has recently been postulated to actively contribute to tumor initiation and progression. This Editorial highlights the role of local paracrine interactions between adipocytes and colon cancer cells. Discovery of signalling pathways activated by tumor resident adipocytes in colon cancer will allow better understanding of carcinogenesis and provide potential therapeutic targets.