A role of ghrelin in canine mammary carcinoma cells proliferation, apoptosis and migration

BMC Veterinary Research

Research Article

Izabella Dolka¹  Magdalena Król²  Kinga Majchrzak²  Tomasz Motyl²  Karol M Pawłowski²  Joanna Mucha²  Emilia J Orzechowska³ 

[1] Department of Pathology and Veterinary Diagnostics, Faculty of Veterinary Medicine, Warsaw University of Life Sciences - WULS, Nowoursynowska 159, 02-776, Warsaw, Poland;Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences - WULS, Nowoursynowska 159, 02-776, Warsaw, Poland;Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences - WULS, Nowoursynowska 159, 02-776, Warsaw, Poland;Department of Molecular Biology, Faculty of Biology, Warsaw University, Miecznikowa 1, Warsaw, Poland;

关键词: Canine mammary carcinoma;    Ghrelin;    Growth hormone secretagogue receptor;   

DOI  :  10.1186/1746-6148-8-170

 received in 2012-05-11, accepted in 2012-09-20,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundGhrelin is a natural ligand of the growth hormone secretagogue receptor (GHS-R). They are often co-expressed in multiple human tumors and related cancer cell lines what can indicate that the ghrelin/GHS-R axis may have an important role in tumor growth and progression. However, a role of ghrelin in canine tumors remains unknown. Thus, the aim of our study was two-fold: (1) to assess expression of ghrelin and its receptor in canine mammary cancer and (2) to examine the effect of ghrelin on carcinoma cells proliferation, apoptosis, migration and invasion. The expression of ghrelin and its receptor in canine mammary cancer tissues and cell lines (isolated from primary tumors and their metastases) was examined using Real-time qPCR and immunohistochemistry. For apoptosis analysis the Annexin V and propidium iodide dual staining was applied whereas cell proliferation was evaluated by MTT assay and BrdU incorporation test. The influence of ghrelin on cancer cells migration and invasion was assessed using Boyden chamber assays and wound healing assay.ResultsThe highest expression of ghrelin was observed in metastatic cancers whereas the lowest expression of ghrelin receptor was detected in tumors of the 3rd grade of malignancy. Higher expression of ghrelin and its receptor was detected in cancer cell lines isolated from metastases than in cell lines isolated from primary tumors. In vitro experiments demonstrated that exposure to low doses of ghrelin stimulates cellular proliferation, inhibits apoptosis and promotes motility and invasion of canine mammary cancer cells. Growth hormone secretagogue receptor inhibitor ([D-Lys3]-GHRP6) as well as RNA interference enhances early apoptosis.ConclusionThe presence of ghrelin and GHS-R in all of the examined canine mammary tumors may indicate their biological role in cancer growth and development. Our experiments conducted in vitro confirmed that ghrelin promotes cancer development and metastasis.

【 授权许可】

Unknown   
© Majchrzak et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.