Mutual impact of adipocytes and colorectal cancer cells growing in co-culture conditions

Abstract

Background: Colorectal cancer (CRC) is the third most common malignancy worldwide. CRC cells are situated in an adipocyte-rich microenvironment, which leads to interactions between adipocytes and CRC cells. Upon exposure to cancer cells, adipocytes transform into cancer-associated adipocytes (CAAs), and as a result, they gain features that promote tumor progression. The aim of this research was to shed more light on the detailed role of interactions between adipocytes and CRC cells associated with cancer progression in the context of these alterations.

Methods: To implement adipocyte-CRC cell interaction, a co-culture model was applied. The analyses mainly focused on the metabolic modifications within CAAs and CRC cells, as well as the proliferation and migration potential of CRC cells. The impact of CRC on adipocytes was investigated by qRT-PCR analysis and Oil Red O staining. Proliferation and migration of CRC cells upon co-culture were tested with videomicroscopy, XTT, and a wound healing assay. Metabolic changes within CAAs and CRC cells were investigated based on lipid droplet formation, cell cycle analysis, gene and protein expression by qRT-PCR, and western blotting techniques.

Results: CRC cells induced reprogramming of adipocytes into CAAs, which was connected with downregulation of lipid droplet formation in CAAs and alteration in adipocyte features. CAAs showed decreased metabolism-related gene expression, phosphorylation of Akt, ERK kinases, STAT3, and lactate secretion in comparison to the control. CAAs also promoted the migration, proliferation, and lipid droplet accumulation of CRC cells. After co-culturing with adipocytes, there was a shift to the G2/M phase of the cell cycle according to the differences in cyclin expression.

Conclusion: There are complex bidirectional interactions between adipocytes and CRC cells that may be connected with the induction of CRC cell progression. Video Abstract.

Keywords: Adipokines; Cancer-associated adipocytes (CAAs); Colorectal cancer (CRC); Lipid droplets; Metabolic reprogramming; Tumor microenvironment (TME).