Increased Obesity-Associated Circulating Levels of the Extracellular Matrix Proteins Osteopontin, Chitinase-3 Like-1 and Tenascin C Are Associated with Colon Cancer.
BACKGROUND
Excess adipose tissue represents a major risk factor for the development of colon cancer with inflammation and extracellular matrix (ECM) remodeling being proposed as plausible mechanisms. The aim of this study was to investigate whether obesity can influence circulating levels of inflammation-related extracellular matrix proteins in patients with colon cancer (CC), promoting a microenvironment favorable for tumor growth.


METHODS
Serum samples obtained from 79 subjects [26 lean (LN) and 53 obese (OB)] were used in the study. Enrolled subjects were further subclassified according to the established diagnostic protocol for CC (44 without CC and 35 with CC). Anthropometric measurements as well as circulating metabolites and hormones were determined. Circulating concentrations of the ECM proteins osteopontin (OPN), chitinase-3-like protein 1 (YKL-40), tenascin C (TNC) and lipocalin-2 (LCN-2) were determined by ELISA.


RESULTS
Significant differences in circulating OPN, YKL-40 and TNC concentrations between the experimental groups were observed, being significantly increased due to obesity (P<0.01) and colon cancer (P<0.05). LCN-2 levels were affected by obesity (P<0.05), but no differences were detected regarding the presence or not of CC. A positive association (P<0.05) with different inflammatory markers was also detected.


CONCLUSIONS
To our knowledge, we herein show for the first time that obese patients with CC exhibit increased circulating levels of OPN, YKL-40 and TNC providing further evidence for the influence of obesity on CC development via ECM proteins, representing promising diagnostic biomarkers or target molecules for therapeutics.
Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Pamplona, Spain.|Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA) Pamplona, Spain.
Victoria
V
Catalán
Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Pamplona, Spain.|Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA) Pamplona, Spain.
Javier
J
Gómez-Ambrosi
Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Pamplona, Spain.|Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA) Pamplona, Spain.
Amaia
A
Rodríguez
Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Pamplona, Spain.|Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA) Pamplona, Spain.
Beatriz
B
Ramírez
Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Pamplona, Spain.
Maitane
M
Izaguirre
Department of Surgery, Clínica Universidad de Navarra, Pamplona, Spain.
José Luis
JL
Hernández-Lizoain
Department of Surgery, Clínica Universidad de Navarra, Pamplona, Spain.
Jorge
J
Baixauli
Department of Surgery, Clínica Universidad de Navarra, Pamplona, Spain.
Pablo
P
Martí
CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Pamplona, Spain.|Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA) Pamplona, Spain.|Department of Surgery, Clínica Universidad de Navarra, Pamplona, Spain.
Víctor
V
Valentí
CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Pamplona, Spain.|Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA) Pamplona, Spain.|Department of Anesthesia, Clínica Universidad de Navarra, Pamplona, Spain.
Rafael
R
Moncada
CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Pamplona, Spain.|Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA) Pamplona, Spain.|Department of Endocrinology & Nutrition, Clínica Universidad de Navarra, Pamplona, Spain.
Camilo
C
Silva
CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Pamplona, Spain.|Department of Endocrinology & Nutrition, Clínica Universidad de Navarra, Pamplona, Spain.
Javier
J
Salvador
Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Pamplona, Spain.|Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA) Pamplona, Spain.|Department of Endocrinology & Nutrition, Clínica Universidad de Navarra, Pamplona, Spain.
Gema
G
Frühbeck
D000071451:Chitinase-3-Like Protein 1 / Q000097:blood*; D003110:Colonic Neoplasms / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000097:blood*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood; D053495:Osteopontin / Q000097:blood*; D019063:Tenascin / Q000097:blood*
D000071451:Chitinase-3-Like Protein 1; D016326:Extracellular Matrix Proteins; D019063:Tenascin; D053495:Osteopontin