Decreased Levels of Microfibril-Associated Glycoprotein (MAGP)-1 in Patients with Colon Cancer and Obesity Are Associated with Changes in Extracellular Matrix Remodelling

Objective: The protein microfibril-associated glycoprotein (MAGP)-1 constitutes a crucial extracellular matrix protein. We aimed to determine its impact on visceral adipose tissue (VAT) remodelling during obesity-associated colon cancer (CC).

Methods: Samples obtained from 79 subjects (29 normoponderal (NP) (17 with CC) and 50 patients with obesity (OB) (19 with CC)) were used in the study. Circulating concentrations of MAGP-1 and its gene expression levels () in VAT were analysed. The impact of inflammation-related factors and adipocyte-conditioned media (ACM) on mRNA levels in colon adenocarcinoma HT-29 cells were further analysed. The effects of MAGP-1 in the expression of genes involved in the extracellular matrix (ECM) remodelling and tumorigenesis in HT-29 cells was also explored.

Results: Obesity ( < 0.01) and CC ( < 0.001) significantly decreased gene expression levels in VAT whereas an opposite trend in mRNA levels was observed. Increased mRNA levels of after the stimulation of HT-29 cells with lipopolysaccharide (LPS) ( < 0.01) and interleukin (IL)-4 ( < 0.01) together with a downregulation ( < 0.05) after hypoxia mimicked by CoCl treatment was observed. MAGP-1 treatment significantly enhanced the mRNA levels of the ECM-remodelling genes collagen type 6 α3 chain ( ( < 0.05), decorin () ( < 0.01), osteopontin () ( < 0.05) and ( < 0.05). Furthermore, MAGP-1 significantly reduced ( < 0.05) the gene expression levels of prostaglandin-endoperoxide synthase 2 (/), a key gene controlling cell proliferation, growth and adhesion in CC. Interestingly, a significant decrease ( < 0.01) in the mRNA levels of in HT-29 cells preincubated with ACM from volunteers with obesity compared with control media was observed. The decreased levels of MAGP-1 in patients with obesity and CC together with its capacity to modulate key genes involved in ECM remodelling and tumorigenesis suggest MAGP-1 as a link between AT excess and obesity-associated CC development.