Obesity and colorectal cancer: role of adipokines in tumor initiation and progression.
Obesity-associated diseases account for a large portion of public health challenges. Among obesity-related disorders, a direct and independent relationship has been ascertained for colorectal cancer (CRC). The evidence that adipocyte hypertrophy and excessive adipose tissue accumulation (mainly visceral) can promote pathogenic adipocyte and adipose tissue-related diseases, has led to formulate the concept of "adiposopathy", defined as adipocyte and adipose tissue dysfunction that contributes to metabolic syndrome. Adipose tissue can, indeed, be regarded as an important and highly active player of the innate immune response, in which cytokine/adipokine secretion is responsible for a paracrine loop between adipocytes and macrophages, thus contributing to the systemic chronic low-grade inflammation associated with visceral obesity, which represents a favorable niche for tumor development. The adipocyte itself participates as a central mediator of this inflammatory response in obese individuals by secreting hormones, growth factors and proinflammatory cytokines, which are of particular relevance for the pathogenesis of CRC. Among adipocyte-secreted hormones, the most relevant to colorectal tumorigenesis are adiponectin, leptin, resistin and ghrelin. All these molecules have been involved in cell growth and proliferation, as well as tumor angiogenesis and it has been demonstrated that their expression changes from normal colonic mucosa to adenoma and adenocarcinoma, suggesting their involvement in multistep colorectal carcinogenesis. These findings have led to the hypothesis that an unfavorable adipokine profile, with a reduction of those with an anti-inflammatory and anti-cancerous activity, might serve as a prognostic factor in CRC patients and that adipokines or their analogues/antagonists might become useful agents in the management or chemoprevention of CRC.
Silvia Riondino, Mario Roselli, Department of Systems Medicine, Medical Oncology, Tor Vergata Clinical Center, University of Rome "Tor Vergata", 00133 Rome, Italy.
Silvia
S
Riondino
Silvia Riondino, Mario Roselli, Department of Systems Medicine, Medical Oncology, Tor Vergata Clinical Center, University of Rome "Tor Vergata", 00133 Rome, Italy.
Mario
M
Roselli
Silvia Riondino, Mario Roselli, Department of Systems Medicine, Medical Oncology, Tor Vergata Clinical Center, University of Rome "Tor Vergata", 00133 Rome, Italy.
Raffaele
R
Palmirotta
Silvia Riondino, Mario Roselli, Department of Systems Medicine, Medical Oncology, Tor Vergata Clinical Center, University of Rome "Tor Vergata", 00133 Rome, Italy.
David
D
Della-Morte
Silvia Riondino, Mario Roselli, Department of Systems Medicine, Medical Oncology, Tor Vergata Clinical Center, University of Rome "Tor Vergata", 00133 Rome, Italy.
Patrizia
P
Ferroni
Silvia Riondino, Mario Roselli, Department of Systems Medicine, Medical Oncology, Tor Vergata Clinical Center, University of Rome "Tor Vergata", 00133 Rome, Italy.
Fiorella
F
Guadagni
D054392:Adipokines / Q000378:metabolism*; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D012307:Risk Factors; D015398:Signal Transduction; D057170:Translational Research, Biomedical
D054392:Adipokines; D018836:Inflammation Mediators
Adiponectin; Colorectal cancer; Cytokines; Ghrelin; Inflammation; Leptin; Obesity; Resistin