Leptin stimulates the proliferation of human colon cancer cells in vitro but does not promote the growth of colon cancer xenografts in, nude mice or intestinal tumorigenesis in Apcmin/+ mice

Aparicio, T.; Kotelevets, L.; Tsocas, A.; Laigneau, J.-P.; Sobhani, I.; Chastre, E.; Lehy, T.
August 2005
Gut;Aug2005, Vol. 54 Issue 8, p1136
Academic Journal
Background and aims: Leptin, the product of the ob gene, has been suggested to increase the risk of colon cancer. However, we have shown that although leptin stimulates epithelial cell proliferation it reduces the development of carcinogen induced preneoplastic lesions in the rat colon. Here, we explored the effect of leptin in vitro on proliferation of human colon cancer cells, and in vivo on the growth of HT-29 xenografts in nude mice and the development of intestinal tumours in ApcMin/+ mice. Methods: Proliferation of HT-29, LoVo, Caco2, and SW 480 cells was assessed in the absence or presence of leptin (20-500 ng/ml) by ³H-thymidine incorporation and cell count. Leptin (800 μg/kg/day) or its vehicle was delivered for four weeks to nude mice, inoculated with HT-29 cells on day 0, and for six weeks to ApcMin/+ mice. Results: Leptin dose dependently stimulated cell DNA synthesis and growth in all cell lines. In nude mice, leptin caused a 4.3-fold increase in plasma leptin levels compared with pair fed controls. This hyperleptinaemia, despite leptin receptor expression in tumours, did not induce significant variation in tumour volume or weight. Tumour Ki-67 index was even inhibited. In leptin treated ApcMin/+ mice, a 2.4- fold increase in plasma leptin levels did not modify the number, size, or distribution of intestinal adenomas compared with pair fed controls. Conclusions: Leptin acts as a growth factor on colon cancer cells in vitro but does not promote tumour growth in vivo in the two models tested. These findings do not support a pivotal role for hyperleptinaemia in intestinal carcinogenesis.


Related Articles

  • Impact of obesity and leptin on protein expression profiles in mouse colon. Padidar, Sara; Farquharson, Andrew; Williams, Lynda; Hoggard, Nigel; Reid, Martin; Duncan, Gary; Drew, Janice; Farquharson, Andrew J; Williams, Lynda M; Reid, Martin D; Duncan, Gary J; Drew, Janice E // Digestive Diseases & Sciences;Apr2011, Vol. 56 Issue 4, p1028 

    Background: Elevated leptin levels in obesity are associated with increased risk of colon pathology, implicating leptin signaling in colon disease. However, leptin-regulated processes in the colon are currently uncharacterized. Previously, we demonstrated that leptin receptors are...

  • Impact of p27mt gene on transplantation model of human colorectal cancer in nude mice. Jun Chen; Wu-Hua Ding; Guang-Xin Lu; Shao-Yong Xu; Yang, Vincent W. // World Journal of Gastroenterology;1/21/2009, Vol. 15 Issue 3, p369 

    AIM: To investigate the inhibitory and anti-metastatic effect of mutant p27 gene (p27mt) on the growth of colorectal cancer xenografts in nude mice and its underlying mechanism. METHODS: Inhibitory effect of p27mt gene on the growth of colorectal cancer xenografts was determined by measurement...

  • Preclinical pharmacokinetics and in vitro metabolism of brivanib (BMS-540215), a potent VEGFR2 inhibitor and its alanine ester prodrug brivanib alaninate. Marathe, Punit H.; Kamath, Amrita V.; Yueping Zhang; D'Arienzo, Celia; Bhide, Rajeev; Fargnoli, Joseph // Cancer Chemotherapy & Pharmacology;Dec2009, Vol. 65 Issue 1, p55 

    Brivanib alaninate is a prodrug of brivanib (BMS-540215), a potent oral VEGFR-2 inhibitor and is currently in development for the treatment of hepatocellular and colon carcinomas. In vitro and in vivo studies were conducted to characterize the preclinical pharmacokinetics and disposition of...

  • Transgenic Complementation of Leptin-Receptor Deficiency. Kowalski, Timothy J.; Shun-Mei Liu; Leibel, Rudolph L.; Chua, Jr., Streamson C. // Diabetes;Feb2001, Vol. 50 Issue 2, p425 

    Mice homozygous for the Lepr[sup db3J] (db[sup 3J]) mutation are null for all known isoforms of the leptin receptor (LEPR). These animals are obese, hyperphagic, cold intolerant, insulin resistant, and infertile. Mice homozygous for the Lepr[sup db] (db) mutation (lacking the B isoform only)...

  • Inhibitory effects of baicalin on orthotopic xenografts of colorectal cancer cells that are deficient in a mismatch repair gene in nude mice. Yang, Bo-Lin; Chen, Hong-Jin; Chen, Yu-Gen; Gu, Yun-Fei; Zhang, Shu-Peng; Lin, Qiu; Sun, Yu // International Journal of Colorectal Disease;Apr2013, Vol. 28 Issue 4, p547 

    Objective: The aim of this article is to study the inhibitory effects of baicalin on the growth and metastasis of orthotopic xenografts consisting of human HCT-116 colorectal cancer cells that are deficient in the mismatch repair gene hMLH1 in nude mice. Methods: A fluorescent orthotopic...

  • Cholecystokinin-mediated suppression of feeding involves the brainstem melanocortin system. Fan, Wei; Ellacott, Kate L. J.; Halatchev, Ilia G.; Takahashi, Kanji; Yu, Pinxuan; Cone, Roger D. // Nature Neuroscience;Apr2004, Vol. 7 Issue 4, p335 

    Hypothalamic pro-opiomelanocortin (POMC) neurons help regulate long-term energy stores. POMC neurons are also found in the nucleus tractus solitarius (NTS), a region regulating satiety. We show here that mouse brainstem NTS POMC neurons are activated by cholecystokinin (CCK) and feeding-induced...

  • Of Mice and Mass. Neporent, Liz // Joe Weider's Muscle & Fitness Hers;Nov2003, Vol. 4 Issue 8, p112 

    Deals with the link between leptin and obesity, based on studies conducted on mice. Role of leptin in regulating body fat; Impact of weight loss on leptin levels and leptin resistance.

  • Immunochemotherapy of human colon carcinoma xenografts in nude mice using combinations of idarubicin-monoclonal antibody conjugates. Smyth, Mark J.; Foster, Hamish Mca.; Andrew, Sarah M.; Teh, Jin. Ghee; Krauer, Kenia; Mckenzie, Ian F.C.; Pietersz, Geoffrey A. // Immunology & Cell Biology;Jun1993, Vol. 71 Issue 3, p167 

    Tumour cell heterogeneity is probably a principal cause of treatment failure and represents a formidable barrier for effective antibody-targeted chemotherapy. Idarubicin (Ida), a more potent and less cardiotoxic analogue of daunomycin, has been demonstrated to specifically target and eradicate...

  • High Fragmentation Characterizes Tumour-Derived Circulating DNA. Mouliere, Florent; Robert, Bruno; Peyrotte, Erika Arnau; Del Rio, Maguy; Marc Ychou; Molina, Franck; Gongora, Celine; Thierry, Alain R. // PLoS ONE;2011, Vol. 6 Issue 9, p1 

    Background: Circulating DNA (ctDNA) is acknowledged as a potential diagnostic tool for various cancers including colorectal cancer, especially when considering the detection of mutations. Certainly due to lack of normalization of the experimental conditions, previous reports present many...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics