Expression of leptin and leptin receptors in colorectal cancer—an immunohistochemical study (original) (raw)
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Brazilian Journal of Medical and Biological Research, 2013
The objective of the present study was to investigate the effect of leptin on the progression of colorectal carcinoma to metastatic disease by analyzing the serum leptin concentration and Ob-R gene expression in colon cancer tissues. Tissue samples were obtained from 31 patients who underwent surgical resection for colon (18 cases) and metastatic colon (13 cases) cancer. Serum leptin concentration was determined by an enzyme-linked immunosorbent assay (ELISA) and Ob-R mRNA expression by real-time polymerase chain reaction (RT-PCR) for both groups. ELISA data were analyzed by the Student t-test and RT-PCR data were analyzed by the Mann-Whitney U-test. RT-PCR results demonstrated that mRNA expression of Ob-R in human metastatic colorectal cancer was higher than in local colorectal cancer tissues. On the other hand, mean serum leptin concentration was significantly higher in local colorectal cancer patients compared to patients with metastatic colorectal cancer. The results of the present study suggest a role for leptin in the progression of colon cancer to metastatic disease without weight loss. In other words, significantly increased Ob-R mRNA expression and decreased serum leptin concentration in patients with metastatic colon cancer indicate that sensitization to leptin activity may be a major indicator of metastasis to the colon tissue and the determination of leptin concentration and leptin gene expression may be used to aid the diagnosis.
Journal of B.U.ON. : official journal of the Balkan Union of Oncology, 2019
PURPOSE Carcinoma of the colon occurs quite more often in obese than in healthy people. The key molecule in the development of obesity is leptin, a product of Ob gene that expresses its effects through a specific receptor (LEPR), so our goal was to investigate the expression of LEPR in colorectal carcinoma and the association of their expression with neoangiogenesis, with local/regional and distant metastases and with tumor stage according to the Astler-Coller classification. METHODS In the paraffin blocks taken from 75 patients treated for colorectal cancer, 3-4 μm thick cuts were made using routine hematoxylin-eosin (HE) and immunohistochemical ABC methods with anti-LEPR and anti-CD105 antibodies. After quantitative analysis of LEPR expression, the microvascular density per mm2 was calculated stereometrically. For the statistical processing, the SPSS software (version 13.0) was used. RESULTS Pronounced expression of LEPR in stages B1 and B2 was present in 9.1% and in 16% of the ca...
Leptin Signaling in Obesity and Colorectal Cancer
International Journal of Molecular Sciences
Obesity and colorectal cancer (CRC) are among the leading diseases causing deaths in the world, showing a complex multifactorial pathology. Obesity is considered a risk factor in CRC development through inflammation, metabolic, and signaling processes. Leptin is one of the most important adipokines related to obesity and an important proinflammatory marker, mainly expressed in adipose tissue, with many genetic variation profiles, many related influencing factors, and various functions that have been ascribed but not yet fully understood and elucidated, the most important ones being related to energy metabolism, as well as endocrine and immune systems. Aberrant signaling and genetic variations of leptin are correlated with obesity and CRC, with the genetic causality showing both inherited and acquired events, in addition to lifestyle and environmental risk factors; these might also be related to specific pathogenic pathways at different time points. Moreover, mutation gain is a cruci...
Annals of Oncology, 2007
Background: The obesity hormone, leptin, has been found to play a role in development and proliferation of normal and malignant tissues. Leptin activity is mediated through the leptin receptor (ObR) that is often expressed in different human cancer cells. Previously, we found that the expression of leptin and ObR can be stimulated by hypoxia-mimetic agents. The aim of this study was to analyze the abundance of and relationships among leptin, ObR and hypoxia-inducible factor-1a (HIF-1a, transcriptional regulator) in human colorectal cancer.
Turkish Journal of Biochemistry, 2016
Objective: The expressions of leptin and its receptor (ObR) have been observed in human gastric cancer (GC) tissue. Leptin can promote the proliferation of GC cells. However, the correlation between leptin and ObR expressions in GC and the role of gastric ObR protein levels in patients with GC is still unclear. This study aimed to evaluate the relationship between leptin, gastric ObR protein and soluble leptin receptor (sObR) levels and whether their possible role of indicator in GC.Methods: Serum leptin, gastric leptin and serum sObR concentrations were determined in 30 male patients with GC and 25 male dyspeptic subjects by enzyme linked immunosorbent assay. We analysed the expression of gastric ObR levels in endoscopically obtained biopsy samples by using Western Blotting method.Results: Compared with controls, patients had lower serum leptin and higher gastric tissue leptin levels. sObR protein concentrations of patients were detected significantly higher, gastric ObR protein ex...
Data from Involvement of the Leptin Receptor in the Immune Response in Intestinal Cancer
The incidence of colorectal cancers (CRC) may be influenced by environmental factors, including nutrition. The role of peptides regulating food intake in controlling the growth and recurrence of human tumors is controversial. Leptin, a cytokine-like peptide, regulates food intake. We investigated the expression of leptin and its receptor in 171 consecutive patients (78 female and 93 male; 71 years) with CRC. Leptin concentrations in the serum (ELISA) were determined before tumor removal. ObRb was characterized in tumors and normal homologous tissues and culture cells (HT29, HCT116, and HCT116 with a transferred chromosome 3) by using immunocytochemistry, immunohistochemistry, reverse transcription-PCR (RT-PCR), and Western blotting. Microsatellite instability (MSI) phenotype was characterized by immunohistochemistry and pentaplex PCR. mRNAs of cytokines and chemokines were quantified in tumors and in normal homologous tissues (RT-PCR) in 43 patients. Adequate statistical tests, incl...
Carcinogenesis, 2009
We investigated the role of leptin receptor (Ob-R) and its relationship with phosphatidylinositol 3-kinase (PI3K)/AKT activation in colorectal carcinomas (CRCs) tissues followed by in vitro studies using a panel of CRC cell lines. Obesity serves an important risk factor of several cancers including CRC that ranks as the second most common cancer in Saudi Arabia. High levels of adipokine leptin (Ob) and its Ob-R are seen in obesity and also in various carcinomas including CRC. We investigated the proliferative and antiapoptotic effect of Ob on human CRC cell lines Caco-2, HT-29 and SW-840 and the role of PI3K/AKT-signaling pathway in mediating these actions. Then the expression of Ob-R and its relationship with clinicopathological features was analyzed in 448 CRC, 229 normal colon mucosa and 24 colorectal adenomas using tissue microarray technology. Treatment with Ob resulted in increased proliferation of CRC cell lines and involved activation of PI3K/AKT-signaling pathway. Pretreatment with Ob-R small interfering RNA or PI3K inhibitor inhibited these responses. Ob-R was significantly overexpressed in primary CRC relative to adenomas and normal colonic mucosa. In primary CRC, Ob-R significantly correlated with Ob expression, early stage and well-differentiated tumors. Intriguingly, patient with Ob-R positive tumors showed significantly better overall survival (P 5 0.0098). Ob plays a critical role in CRC carcinogenesis through PI3K/AKT pathway via Ob-R. Ob-R is a prognostic marker associated with better survival.
Obesity and colon cancer: Does leptin provide a link?
International Journal of Cancer, 2004
Obesity, a risk factor for colorectal cancer, is associated with elevated serum levels of leptin, the adipocyte-derived hormone, and insulin. Experimental and epidemiologic studies have indicated a role for insulin in the pathogenesis of colon cancer, and recent experimental studies have suggested a similar role for leptin. In a case-control study nested in the Janus Biobank, Norway, we measured serum levels of leptin and C-peptide (a marker of pancreatic insulin secretion) in cryopreserved prediagnostic sera from men (median age, 45 years) who were diagnosed with cancer of the colon (n ؍ 235) or rectum (n ؍ 143) after blood collection (median time, 17 years), and among 378 controls matched for age and date of blood collection. Conditional logistic regression analyses showed an approximately 3-fold increase in colon cancer risk with increasing concentrations of leptin up to an odds ratio (OR) of 2.72 (95% CI ؍ 1.44 -5.12) for top vs. bottom quartile (p trend ؍ 0.008). The corresponding OR for C-peptide was 1.81 (95% CI ؍ 0.67-4.86; p trend ؍ 0.19). The risk estimates remained unchanged after mutual adjustment. No association of hormone levels with rectal cancer risk was found. Reproducibility of hormone measurements assessed by intraclass coefficients (ICCs) for paired samples taken 1 year apart was high for leptin (ICC ؍ 0.82) but lower for C-peptide (ICC ؍ 0.30). Our results suggest that leptin is a risk factor for colon cancer, and that leptin may provide a link between obesity and colon cancer. Leptin may be directly involved in colon tumorigenesis or it may serve as a sensitive and robust marker of an obesity-induced adverse endocrine environment. Only weak support for an association of insulin with colon cancer was found.