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.

Unlocking the paracrine crosstalk: adipocyte-derived factors affect carbonic anhydrase IX expression in colon and breast cancer cells

“…In comparison to mono-cultured HCT116 and BT-20 cells, upregulated expression of CA IX was revealed after co-cultivation with 3T3-L1 adipocytes. In line with our results with CA IX, higher expression levels of GLUT1 and GLUT3 in colon cancer cells (HCT116 and LS180) co-cultivated with 3T3-L1 adipocytes were observed by Olszanska et al [31], however, their co-cultivation experiments were performed only in normoxia. In addition to 3T3-L1 adipocytes, we observed increased expression of CA IX after co-cultivation with additional adipocyte models iWAT and hMADS which have a more pronounced effect in normoxia and hypoxia, respectively.…”

“…Given the close relationship between obesity and tumor progression, adipocytes are considered to be crucial components of TME. Previous studies have identified alterations in adipocyte features upon exposure to cancer cells, resulting in their transformation into cancer-associated adipocytes (CAAs) [5,[29][30][31]. Such interplay between adipocytes and cancer cells could be particularly relevant at the invasive front of tumors where both cell types are in tight contact and where adipocytes could provide a wide array of effectors, e.g., adipokines, lipids, and exosomes [6].…”

“…Previous studies reported that adipocytes and adipocyte-secreted factors could affect the biological properties (e.g., enhanced motility) and molecular characteristics of cancer cells (e.g., expression of genes associated with a more aggressive phenotype) [5,31,34,35], although the nature of these factors is still under investigation. As mentioned before, CM-treated colon and breast cancer cells exhibited increased expression of CA IX in normoxia.…”