Up-regulation of the novel proinflammatory adipokines lipocalin-2, chitinase-3 like-1 and osteopontin as well as angiogenic-related factors in visceral adipose tissue of patients with colon cancer.
BACKGROUND
Obesity is widely recognised as an important risk factor for colorectal cancer (CC).


OBJECTIVE
The study aimed to evaluate the effect of CC on circulating concentrations and gene expression levels of inflammatory and angiogenesis-related factors in human visceral adipose tissue (VAT).


METHODS
VAT biopsies were obtained from 18 healthy individuals and 11 patients with CC. Real-time polymerase chain reactions were performed to quantify gene expression levels and zymographic analyses were used to determine the activity of matrix metalloproteinases (MMPs).


RESULTS
Patients with CC exhibited increased mRNA expression levels of lipocalin-2 (P=.014), osteopontin (P=.027), tumor necrosis factor-α (TNF-α) (P=.016) and chitinase-3 like-1 (P=.006) compared to control subjects in VAT. Gene expression levels of hypoxia-inducible factor-1 α, vascular endothelial growth factor and MMP-2 were significantly higher (P<.05) in VAT of patients with CC. The expression of insulin-like growth factor I, insulin growth factor binding protein 3 and MMP-9 followed the same trend, although no significant differences were reached. The enzymatic activity of MMP-9 was increased (P<.001) in patients with CC. Furthermore, individuals with CC showed increased (P<.05) circulating concentrations of the inflammatory markers interleukin-6, tumour necrosis factor α and hepatocyte growth factor, whereas levels of the anti-inflammatory adipokine adiponectin were decreased (P<.01).


CONCLUSIONS
These findings represent the first observation that mRNA levels of the novel inflammatory factors lipocalin-2, chitinase-3 like-1 and osteopontin are increased in human VAT of subjects with CC. This observation together with the up-regulation of angiogenic factors suggests that adipokines secreted by VAT may be involved in the development of colon cancer.
Metabolic Research Laboratory, Clínica Universidad de Navarra, 31008 Pamplona, Spain.
Victoria
V
Catalán
Javier
J
Gómez-Ambrosi
Amaia
A
Rodríguez
Beatriz
B
Ramírez
Camilo
C
Silva
Fernando
F
Rotellar
José L
JL
Hernández-Lizoain
Jorge
J
Baixauli
Victor
V
Valentí
Fernando
F
Pardo
Javier
J
Salvador
Gema
G
Frühbeck
D000209:Acute-Phase Proteins / Q000096:biosynthesis*; D054392:Adipokines; D000328:Adult; D000368:Aged; D043925:Angiogenesis Inducing Agents; D000071451:Chitinase-3-Like Protein 1; D002688:Chitinases / Q000096:biosynthesis*; D003110:Colonic Neoplasms / Q000378:metabolism*; D006023:Glycoproteins / Q000096:biosynthesis*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D037102:Lectins / Q000096:biosynthesis*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000096:biosynthesis*; D020782:Matrix Metalloproteinases / Q000096:biosynthesis; D008875:Middle Aged; D053495:Osteopontin / Q000096:biosynthesis*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D000209:Acute-Phase Proteins; D054392:Adipokines; D043925:Angiogenesis Inducing Agents; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C489506:LCN2 protein, human; D037102:Lectins; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D053495:Osteopontin; D002688:Chitinases; D020782:Matrix Metalloproteinases