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

被引：13

作者：

Gomez de Segura, Iranzu ^{[1
]}

Ahechu, Patricia ^{[2
]}

Gomez-Ambrosi, Javier ^{[1
,3
,4
]}

Rodriguez, Amaia ^{[1
,3
,4
]}

Ramirez, Beatriz ^{[1
,3
,4
]}

Becerril, Sara ^{[1
,3
,4
]}

Unamuno, Xabier ^{[1
,3
]}

Mentxaka, Amaia ^{[1
,3
]}

Baixauli, Jorge ^{[2
]}

Valenti, Victor ^{[2
,3
,4
]}

Moncada, Rafael ^{[3
,5
]}

Silva, Camilo ^{[3
,4
,6
]}

Fruhbeck, Gema ^{[1
,3
,4
,6
]}

Catalan, Victoria ^{[1
,3
,4
]}

机构：

[1] Clin Univ Navarra, Metab Res Lab, Pamplona 31008, Spain

[2] Clin Univ Navarra, Dept Surg, Pamplona 31008, Spain

[3] Inst Salud Carlos III, CIBEROBN, Pamplona 31008, Spain

[4] IdiSNA, Obes & Adipobiol Grp, Pamplona 31008, Spain

[5] Clin Univ Navarra, Dept Anesthesia, Pamplona 31008, Spain

[6] Clin Univ Navarra, Dept Endocrinol & Nutr, Pamplona 31008, Spain

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2021年 / 22卷 / 16期

关键词：

obesity; colon cancer; adipose tissue; inflammation; extracellular matrix remodelling; MAGP-1; TGF-beta; EPITHELIAL-MESENCHYMAL TRANSITION; HUMAN ADIPOSE-TISSUE; BREAST-CANCER; PROTEIN MAGP1; INFLAMMATION; MFAP2; PROGRESSION; TGF-BETA-1; REGULATOR; SUPPORTS;

D O I：

10.3390/ijms22168485

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 (MFAP2) in VAT were analysed. The impact of inflammation-related factors and adipocyte-conditioned media (ACM) on MFAP2 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 (p < 0.01) and CC (p < 0.001) significantly decreased MFAP2 gene expression levels in VAT whereas an opposite trend in TGFB1 mRNA levels was observed. Increased mRNA levels of MFAP2 after the stimulation of HT-29 cells with lipopolysaccharide (LPS) (p < 0.01) and interleukin (IL)-4 (p < 0.01) together with a downregulation (p < 0.05) after hypoxia mimicked by CoCl2 treatment was observed. MAGP-1 treatment significantly enhanced the mRNA levels of the ECM-remodelling genes collagen type 6 alpha 3 chain (COL6A3) (p < 0.05), decorin (DCN) (p < 0.01), osteopontin (SPP1) (p < 0.05) and TGFB1 (p < 0.05). Furthermore, MAGP-1 significantly reduced (p < 0.05) the gene expression levels of prostaglandin-endoperoxide synthase 2 (COX2/PTGS2), a key gene controlling cell proliferation, growth and adhesion in CC. Interestingly, a significant decrease (p < 0.01) in the mRNA levels of MFAP2 in HT-29 cells preincubated with ACM from volunteers with obesity compared with control media was observed. Conclusion: 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.

引用

页数：15