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Annals of Oncology 2007 18(Supplement 6):vi116-vi119; doi:10.1093/annonc/mdm238
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© 2007 European Society for Medical Oncology

gastro-intestinal cancer

Expression of the obesity hormone leptin and its receptor correlates with hypoxia-inducible factor-1{alpha} in human colorectal cancer

M Koda1, M Sulkowska1, L Kanczuga-Koda1, S Cascio2,3, G Colucci4, A Russo3, E Surmacz2 and S Sulkowski1,*

1 Department of Pathomorphology, Medical University of Bialystok, Bialystok, Poland
2 Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA, USA
3 Section of Medical Oncology, Department of Surgical and Oncology, Università di Palermo, Palermo
4 Division of Medical Oncology, National Institute of Oncology, Bari, Italy

* Correspondence to: Dr S. Sulkowski, Department of Pathomorphology, Medical University of Bialystok, Waszyngtona 13, 15-269 Bialystok, Poland. Tel: +48-85-7485944; Fax: +48-85-7485944; E-mail: sulek{at}zeus.amb.edu.pl

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-1{alpha} (HIF-1{alpha}, transcriptional regulator) in human colorectal cancer.

Materials and methods: We investigated the expression of leptin, ObR and HIF-1{alpha} in colorectal cancer specimens from 135 patients who underwent curative resection.

Results: Immunoreactivity for leptin, ObR and HIF-1{alpha} protein was observed in 69 of 135 (51.1%), 129 of 135 (95.5%) and 88 of 135 (65.2%) of colorectal cancers, respectively.

Statistically significant positive correlations were noted between leptin and HIF-1{alpha} (P = 0.005, r = 0.243), ObR and HIF-1{alpha} (P < 0.001, r = 0.325) as well as leptin and ObR (P < 0.001, r = 0.426) in the group of all patients as well as in various subgroups depending on clinicopathological features.

Conclusions: The results indicate that the leptin system is overexpressed in human colorectal cancer and this overexpression appears to be associated with the abundance of HIF-1{alpha}.

Key words: colorectal cancer, hypoxia-inducible factor-1{alpha}, leptin, leptin receptor, obesity


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