Abstract
Purpose
The aim of this study was to investigate the role of Li-cadherin in invasion and metastasis in LoVo cells.
Methods
We applied RNA interference mediated downregulation of Li-cadherin expression in LoVo cells. Li-cadherin expression in LoVo cells was examined by semiquantitative polymerase chain reaction, immunofluorescence, western blot, and immunoprecipitation, respectively. Effect of suppression of Li-cadherin expression on cell migration, invasion, and adhesion was detected by wound healing assay, migration assay, invasion assay, and adhesion assay. Expression and activity of MMP-2 and MMP-9 were analyzed by gelatin zymography.
Results
Cell migration, invasion, and adhesion were increased concomitantly with the reduction in Li-cadherin protein expression. Furthermore, downregulation of Li-cadherin expression induced secretion of proMMP-9, active MMP-9 and active MMP-2.
Conclusions
This study suggests that silencing Li-cadherin has positive actions in the processes of LoVo cells invasion and metastasis, and the interactions among MMP-2, MMP-9, and Li-cadherin participate in the multiple steps of invasion and metastasis in LoVo colorectal cancer cells.
Similar content being viewed by others
References
Angres B, Kim L, Jung R, Gessner R, Tauber R (2001) Li-cadherin gene expression during mouse intestinal development. Dev Dyn 221:182–193
Berndorff D, Gessner R, Kreft B, Schnoy N, Lajous-Petter AM, Loch N, Reutter W, Hortsch M, Tauber R (1994) Liver–intestine cadherin: molecular cloning and characterization of a novel Ca(2+)-dependent cell adhesion molecule expressed in liver and intestine. J Cell Biol 125:1353–1369
Boyd D (1996) Invasion and metastasis. Cancer Metastasis Rev 15:77–89
Chen WT (1996) Proteases associated with invadopodia, and their role in degradation of extracellular matrix. Enzyme Protein 49:59–71
Dong W, Yu Q, Xu Y (2007) Altered expression of a Li-cadherin in gastric cancer and intestinal metaplasia. Dig Dis Sci 52:536–542
Dong WG, Yu QF, Xu Y, Fan LF (2008) Li-cadherin is inversely correlated with galectin-3 expression in gastric cancer. Dig Dis Sci 53:1811–1817
Efstathiou JA, Noda M, Rowan A, Dixon C, Chinery R, Jawhari A, Hattori T, Wright NA, Bodmer WF, Pignatelli M (1998) Intestinal trefoil factor controls the expression of the adenomatous polyposis coli–catenin and the E-cadherin–catenin complexes in human colon carcinoma cells. Proc Natl Acad Sci U S A 95:3122–3127
German NS, Johanning GL (1997) Eicosapentaenoic acid and epidermal growth factor modulation of human breast cancer cell adhesion. Cancer Lett 118:95–100
Gessner R, Tauber R (2000) Intestinal cell adhesion molecules liver–intestine cadherin. Ann N Y Acad Sci 915:136–143
Grotzinger C, Kneifel J, Patschan D, Schnoy N, Anagnostopoulos I, Faiss S, Tauber R, Wiedenmann B, Gessner R (2001) LI-cadherin: a marker of gastric metaplasia and neoplasia. Gut 49:73–81
Hirohashi S (1998) Inactivation of the E-cadherin-mediated cell adhesion system in human cancers. Am J Pathol 153:333–339
Hirohashi S, Kanai Y (2003) Cell adhesion system and human cancer morphogenesis. Cancer Sci 94:575–581
Huber O, Korn R, McLaughlin J, Ohsugi M, Herrmann BG, Kemler R (1996) Nuclear localization of beta-catenin by interaction with transcription factor LEF-1. Mech Dev 59:3–10
Kleiner DE, Stetler-Stevenson WG (1999) Matrix metalloproteinases and metastasis. Cancer Chemother Pharmacol 43(Suppl):S42–S51
Kleinman HK, McGarvey ML, Hassell JR, Star VL, Cannon FB, Laurie GW, Martin GR (1986) Basement membrane complexes with biological activity. Biochemistry 25:312–318
Ko S, Chu KM, Luk JM, Wong BW, Yuen ST, Leung SY, Wong J (2004) Overexpression of LI-cadherin in gastric cancer is associated with lymph node metastasis. Biochem Biophys Res Commun 319:562–568
Kreft B, Berndorff D, Bottinger A, Finnemann S, Wedlich D, Hortsch M, Tauber R, Gessner R (1997) Li-cadherin-mediated cell–cell adhesion does not require cytoplasmic interactions. J Cell Biol 136:1109–1121
Liotta LA, Steeg PS, Stetler-Stevenson WG (1991) Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell 64:327–336
Mook OR, Frederiks WM, Van Noorden CJ (2004) The role of gelatinases in colorectal cancer progression and metastasis. Biochim Biophys Acta 1705:69–89
Saiki I (1997) Cell adhesion molecules and cancer metastasis. Jpn J Pharmacol 75:215–242
Stemmler MP (2008) Cadherins in development and cancer. Mol Biosyst 4:835–850
Takamura M, Sakamoto M, Ino Y, Shimamura T, Ichida T, Asakura H, Hirohashi S (2003) Expression of liver–intestine cadherin and its possible interaction with galectin-3 in ductal adenocarcinoma of the pancreas. Cancer Sci 94:425–430
Takamura M, Ichida T, Matsuda Y, Kobayashi M, Yamagiwa S, Genda T, Shioji K, Hashimoto S, Nomoto M, Hatakeyama K, Ajioka Y, Sakamoto M, Hirohashi S, Aoyagi Y (2004) Reduced expression of liver–intestine cadherin is associated with progression and lymph node metastasis of human colorectal carcinoma. Cancer Lett 212:253–259
Takeichi M (1993) Cadherins in cancer: implications for invasion and metastasis. Curr Opin Cell Biol 5:806–811
Takeichi M (1995) Morphogenetic roles of classic cadherins. Curr Opin Cell Biol 7:619–627
Wang XQ, Luk JM, Leung PP, Wong BW, Stanbridge EJ, Fan ST (2005) Alternative mRNA splicing of liver intestine-cadherin in hepatocellular carcinoma. Clin Cancer Res 11:483–489
Yagi T, Takeichi M (2000) Cadherin superfamily genes: functions, genomic organization, and neurologic diversity. Genes Dev 14:1169–1180
Acknowledgments
We thank Ph.D. Dian Gao (Medical College, Nanchang University) for excellent technical assistance.
Conflict of interest statement
Authors declare that the manuscript is submitted on behalf of all authors. None of the material in this manuscript has been published previously in any form and none of the material is currently under consideration for publication elsewhere other than noted in the covering letter to the editor.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Yu, QF., Dong, WG. & Ren, JL. Knockdown of Li-cadherin increases metastatic behaviors of LoVo cells. J Cancer Res Clin Oncol 136, 1641–1649 (2010). https://doi.org/10.1007/s00432-010-0822-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00432-010-0822-y