Leptin-induced adhesion and invasion in colorectal cancer cell lines

Yoon,Kyung-Won; Park,Seon-Young; Kim,Ji-Young; Lee,Su-Mi; Park,Chang‑Hwan; Cho,Sung-Bum; Lee,Wan-Sik; Joo,Young-Eun; Lee,Jae‑Hyuk; Kim,Hyun‑Soo; Choi,Sung-Kyu; Rew,Jong-Sun

doi:10.3892/or.2014.3128

Leptin-induced adhesion and invasion in colorectal cancer cell lines

Authors:
- Kyung-Won Yoon
- Seon-Young Park
- Ji-Young Kim
- Su-Mi Lee
- Chang‑Hwan Park
- Sung-Bum Cho
- Wan-Sik Lee
- Young-Eun Joo
- Jae‑Hyuk Lee
- Hyun‑Soo Kim
- Sung-Kyu Choi
- Jong-Sun Rew
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Affiliations: Department of Internal Medicine, Chonnam National University Medical School, Dong-ku, Gwangju 501-757, Republic of Korea
Published online on: April 3, 2014 https://doi.org/10.3892/or.2014.3128
Pages: 2493-2498

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Abstract

Leptin, which is encoded by the obese gene, is a multifunctional neuroendocrine peptide that regulates appetite, bone formation, reproductive function and angiogenesis. The aims of the present study were to investigate the expression of leptin in 80 patients with colorectal cancer (CRC) and to determine the effects of leptin on the malignant properties of CRC cells. We evaluated the expression of leptin in tissues of 80 patients with CRC. Suspension cultures were used to isolate CRC stem cells following pretreatment with leptin. We analyzed the effects of leptin on the adhesion and invasive capacities of CRC cell lines. The effects of leptin on JAK and ERK activation were examined using western blotting. Leptin expression was associated with CRC progression and increased the number and size of spheroid formation by CRC cell lines. Leptin enhanced cell invasion and adhesion and activated JAK and ERK signaling in the CRC cell lines. The present study demonstrated that leptin influences the growth and survival of CRC stem cells and regulates adhesion and invasion of colorectal carcinoma through activation of the JAK and ERK signaling pathways.

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1	Jemal A, Siegel R, Ward E, et al: Cancer statistics, 2006. CA Cancer J Clin. 56:106–130. 2006. View Article : Google Scholar
2	Renehan AG, Tyson M, Egger M, Heller RF and Zwahlen M: Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet. 371:569–578. 2008. View Article : Google Scholar : PubMed/NCBI
3	Calle EE and Thun MJ: Obesity and cancer. Oncogene. 23:6365–6378. 2004. View Article : Google Scholar
4	Amemori S, Ootani A, Aoki S, et al: Adipocytes and preadipocytes promote the proliferation of colon cancer cells in vitro. Am J Physiol Gastrointest Liver Physiol. 292:G923–G929. 2007. View Article : Google Scholar : PubMed/NCBI
5	Halaas JL, Gajiwala KS, Maffei M, et al: Weight-reducing effects of the plasma protein encoded by the obese gene. Science. 269:543–546. 1995. View Article : Google Scholar : PubMed/NCBI
6	Huang L and Li C: Leptin: a multifunctional hormone. Cell Res. 10:81–92. 2000. View Article : Google Scholar
7	Somasundar P, McFadden DW, Hileman SM and Vona-Davis L: Leptin is a growth factor in cancer. J Surg Res. 116:337–349. 2004. View Article : Google Scholar
8	Zhang F, Chen Y, Heiman M and Dimarchi R: Leptin: structure, function and biology. Vitam Horm. 71:345–372. 2005. View Article : Google Scholar : PubMed/NCBI
9	Garofalo C and Surmacz E: Leptin and cancer. J Cell Physiol. 207:12–22. 2006. View Article : Google Scholar
10	Pai R, Lin C, Tran T and Tarnawski A: Leptin activates STAT and ERK2 pathways and induces gastric cancer cell proliferation. Biochem Biophys Res Commun. 331:984–992. 2005. View Article : Google Scholar : PubMed/NCBI
11	Rose DP, Komninou D and Stephenson GD: Obesity, adipocytokines, and insulin resistance in breast cancer. Obes Rev. 5:153–165. 2004. View Article : Google Scholar : PubMed/NCBI
12	Choi JH, Park SH, Leung PC and Choi KC: Expression of leptin receptors and potential effects of leptin on the cell growth and activation of mitogen-activated protein kinases in ovarian cancer cells. J Clin Endocrinol Metab. 90:207–210. 2005. View Article : Google Scholar : PubMed/NCBI
13	Somasundar P, Frankenberry KA, Skinner H, et al: Prostate cancer cell proliferation is influenced by leptin. J Surg Res. 118:71–82. 2004. View Article : Google Scholar : PubMed/NCBI
14	Sharma D, Saxena NK, Vertino PM and Anania FA: Leptin promotes the proliferative response and invasiveness in human endometrial cancer cells by activating multiple signal-transduction pathways. Endocr Relat Cancer. 13:629–640. 2006. View Article : Google Scholar
15	Stattin P, Palmqvist R, Söderberg S, et al: Plasma leptin and colorectal cancer risk: a prospective study in Northern Sweden. Oncol Rep. 10:2015–2021. 2003.PubMed/NCBI
16	Stattin P, Lukanova A, Biessy C, et al: Obesity and colon cancer: Does leptin provide a link? Int J Cancer. 109:149–152. 2004. View Article : Google Scholar : PubMed/NCBI
17	Fenton JI, Hursting SD, Perkins SN and Hord NG: Leptin induces an Apc genotype-associated colon epithelial cell chemokine production pattern associated with macrophage chemotaxis and activation. Carcinogenesis. 28:455–464. 2007. View Article : Google Scholar : PubMed/NCBI
18	Fenton JI, Lavigne JA, Perkins SN, et al: Microarray analysis reveals that leptin induces autocrine/paracrine cascades to promote survival and proliferation of colon epithelial cells in an Apc genotype-dependent fashion. Mol Carcinog. 47:9–21. 2008. View Article : Google Scholar
19	Yu F, Yao H, Zhu P, et al: let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell. 131:1109–1123. 2007. View Article : Google Scholar
20	Yamaguchi H, Wyckoff J and Condeelis J: Cell migration in tumors. Curr Opin Cell Biol. 17:559–564. 2005. View Article : Google Scholar
21	Paik SS, Jang SM, Jang KS, Lee KH, Choi D and Jang SJ: Leptin expression correlates with favorable clinicopathologic phenotype and better prognosis in colorectal adenocarcinoma. Ann Surg Oncol. 16:297–303. 2009. View Article : Google Scholar : PubMed/NCBI
22	Koda M, Sulkowska M, Kanczuga-Koda L, Surmacz E and Sulkowski S: Overexpression of the obesity hormone leptin in human colorectal cancer. J Clin Pathol. 60:902–906. 2007. View Article : Google Scholar : PubMed/NCBI
23	Liu H, Wan D, Pan Z, et al: Expression and biological significance of leptin, leptin receptor, VEGF, and CD34 in colorectal carcinoma. Cell Biochem Biophys. 60:241–244. 2011. View Article : Google Scholar : PubMed/NCBI
24	Bolukbas FF, Kilic H, Bolukbas C, et al: Serum leptin concentration and advanced gastrointestinal cancers: a case controlled study. BMC Cancer. 4:292004. View Article : Google Scholar : PubMed/NCBI
25	Sălăgeanu A, Tucureanu C, Lerescu L, et al: Serum levels of adipokines resistin and leptin in patients with colon cancer. J Med Life. 3:416–420. 2010.PubMed/NCBI
26	Scopelliti A, Cammareri P, Catalano V, Saladino V, Todaro M and Stassi G: Therapeutic implications of cancer initiating cells. Expert Opin Biol Ther. 9:1005–1016. 2009. View Article : Google Scholar
27	Bartucci M, Svensson S, Ricci-Vitiani L, et al: Obesity hormone leptin induces growth and interferes with the cytotoxic effects of 5-fluorouracil in colorectal tumor stem cells. Endocr Relat Cancer. 17:823–833. 2010. View Article : Google Scholar : PubMed/NCBI
28	Singh SK, Hawkins C, Clarke ID, et al: Identification of human brain tumour initiating cells. Nature. 432:396–401. 2004. View Article : Google Scholar : PubMed/NCBI
29	Dey D, Saxena M, Paranjape AN, et al: Phenotypic and functional characterization of human mammary stem/progenitor cells in long term culture. PLoS One. 4:e53292009. View Article : Google Scholar : PubMed/NCBI
30	Todaro M, Alea MP, Di Stefano AB, et al: Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4. Cell Stem Cell. 1:389–402. 2007. View Article : Google Scholar : PubMed/NCBI
31	Fan X, Ouyang N, Teng H and Yao H: Isolation and characterization of spheroid cells from the HT29 colon cancer cell line. Int J Colorectal Dis. 26:1279–1285. 2011. View Article : Google Scholar : PubMed/NCBI
32	Kanwar SS, Yu Y, Nautiyal J, Patel BB and Majumdar AP: The Wnt/β-catenin pathway regulates growth and maintenance of colonospheres. Mol Cancer. 9:2122010.
33	O’Brien CA, Pollett A, Gallinger S and Dick JE: A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 445:106–110. 2007.PubMed/NCBI
34	Uchiyama T, Takahashi H, Sugiyama M, et al: Leptin receptor is involved in STAT3 activation in human colorectal adenoma. Cancer Sci. 102:367–372. 2011. View Article : Google Scholar : PubMed/NCBI
35	Vécsey-Semjén B, Becker KF, Sinski A, et al: Novel colon cancer cell lines leading to better understanding of the diversity of respective primary cancers. Oncogene. 21:4646–4662. 2002.PubMed/NCBI