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Published in: Journal of Hematology & Oncology 1/2013

Open Access 01-12-2013 | Research

L1cam promotes tumor progression and metastasis and is an independent unfavorable prognostic factor in gastric cancer

Authors: Dong-liang Chen, Zhao-lei Zeng, Jing Yang, Chao Ren, De-shen Wang, Wen-jing Wu, Rui-hua Xu

Published in: Journal of Hematology & Oncology | Issue 1/2013

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Abstract

Background

Previous reports have demonstrated that L1cam is aberrantly expressed in various tumors. The potential role of L1cam in the progression and metastasis of gastric cancer is still not clear and needs exploring.

Methods

Expression of L1cam was evaluated in gastric cancer tissues and cell lines by immunohistochemistry and Western blot. The relationship between L1cam expression and clinicopathological characteristics was analyzed. The effects of L1cam on cell proliferation, migration and invasion were investigated in gastric cancer cell lines both in vitro and in vivo. The impact of L1cam on PI3K/Akt pathway was also evaluated.

Results

L1cam was overexpressed in gastric cancer tissues and cell lines. L1cam expression was correlated with aggressive tumor phenotype and poor overall survival in gastric cancer patients. Ectopic expression of L1cam in gastric cell lines significantly promoted cell proliferation, migration and invasion whereas knockdown of L1cam inhibited cell proliferation, migration and invasion in vitro as well as tumorigenesis and metastasis in vivo. The low level of phosphorylated Akt in HGC27 cells was up-regulated after ectopic expression of L1cam, whereas the high level of phosphorylated Akt in SGC7901 cells was suppressed by knockdown of L1cam. Moreover, the migration and invasion promoted by L1cam overexpression in gastric cancer cells could be abolished by either application of LY294002 (a phosphoinositide-3-kinase inhibitor) or knockdown of endogenous Akt by small interfering RNA.

Conclusions

Our study demonstrated that L1cam, overexpressed in gastric cancer and associated with poor prognosis, plays an important role in the progression and metastasis of gastric cancer.
Appendix
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Literature
1.
go back to reference Jemal A, Siegel R, Xu J, Ward E: Cancer statistics, 2010. CA Cancer J Clin. 2010, 60: 277-300. 10.3322/caac.20073.CrossRefPubMed Jemal A, Siegel R, Xu J, Ward E: Cancer statistics, 2010. CA Cancer J Clin. 2010, 60: 277-300. 10.3322/caac.20073.CrossRefPubMed
2.
go back to reference Wang XN, Liang H: Some problems in the surgical treatment of gastric cancer. Chin J Cancer. 2010, 29: 369-373. 10.5732/cjc.009.10629.CrossRefPubMed Wang XN, Liang H: Some problems in the surgical treatment of gastric cancer. Chin J Cancer. 2010, 29: 369-373. 10.5732/cjc.009.10629.CrossRefPubMed
3.
go back to reference Steeg PS: Metastasis suppressors alter the signal transduction of cancer cells. Nat Rev Cancer. 2003, 3: 55-63. 10.1038/nrc967.CrossRefPubMed Steeg PS: Metastasis suppressors alter the signal transduction of cancer cells. Nat Rev Cancer. 2003, 3: 55-63. 10.1038/nrc967.CrossRefPubMed
4.
go back to reference Hohenberger P, Gretschel S: Gastric cancer. Lancet. 2003, 362: 305-315.PubMed Hohenberger P, Gretschel S: Gastric cancer. Lancet. 2003, 362: 305-315.PubMed
5.
go back to reference Lindner J, Rathjen FG, Schachner M: L1 mono- and polyclonal antibodies modify cell migration in early postnatal mouse cerebellum. Nature. 1983, 305: 427-430. 10.1038/305427a0.CrossRefPubMed Lindner J, Rathjen FG, Schachner M: L1 mono- and polyclonal antibodies modify cell migration in early postnatal mouse cerebellum. Nature. 1983, 305: 427-430. 10.1038/305427a0.CrossRefPubMed
6.
go back to reference Brummendorf T, Rathjen FG: Axonal glycoproteins with immunoglobulin- and fibronectin type III-related domains in vertebrates: structural features, binding activities, and signal transduction. J Neurochem. 1993, 61: 1207-1219. 10.1111/j.1471-4159.1993.tb13611.x.CrossRefPubMed Brummendorf T, Rathjen FG: Axonal glycoproteins with immunoglobulin- and fibronectin type III-related domains in vertebrates: structural features, binding activities, and signal transduction. J Neurochem. 1993, 61: 1207-1219. 10.1111/j.1471-4159.1993.tb13611.x.CrossRefPubMed
7.
go back to reference Hortsch M: The L1 family of neural cell adhesion molecules: old proteins performing new tricks. Neuron. 1996, 17: 587-593. 10.1016/S0896-6273(00)80192-0.CrossRefPubMed Hortsch M: The L1 family of neural cell adhesion molecules: old proteins performing new tricks. Neuron. 1996, 17: 587-593. 10.1016/S0896-6273(00)80192-0.CrossRefPubMed
8.
go back to reference Moos M, Tacke R, Scherer H, Teplow D, Fruh K, Schachner M: Neural adhesion molecule L1 as a member of the immunoglobulin superfamily with binding domains similar to fibronectin. Nature. 1988, 334: 701-703. 10.1038/334701a0.CrossRefPubMed Moos M, Tacke R, Scherer H, Teplow D, Fruh K, Schachner M: Neural adhesion molecule L1 as a member of the immunoglobulin superfamily with binding domains similar to fibronectin. Nature. 1988, 334: 701-703. 10.1038/334701a0.CrossRefPubMed
9.
go back to reference Rathjen FG, Schachner M: Immunocytological and biochemical characterization of a new neuronal cell surface component (L1 antigen) which is involved in cell adhesion. EMBO J. 1984, 3: 1-10.PubMedCentralPubMed Rathjen FG, Schachner M: Immunocytological and biochemical characterization of a new neuronal cell surface component (L1 antigen) which is involved in cell adhesion. EMBO J. 1984, 3: 1-10.PubMedCentralPubMed
10.
go back to reference Dahme M, Bartsch U, Martini R, Anliker B, Schachner M, Mantei N: Disruption of the mouse L1 gene leads to malformations of the nervous system. Nat Genet. 1997, 17: 346-349. 10.1038/ng1197-346.CrossRefPubMed Dahme M, Bartsch U, Martini R, Anliker B, Schachner M, Mantei N: Disruption of the mouse L1 gene leads to malformations of the nervous system. Nat Genet. 1997, 17: 346-349. 10.1038/ng1197-346.CrossRefPubMed
11.
go back to reference Debiec H, Christensen EI, Ronco PM: The cell adhesion molecule L1 is developmentally regulated in the renal epithelium and is involved in kidney branching morphogenesis. J Cell Biol. 1998, 143: 2067-2079. 10.1083/jcb.143.7.2067.PubMedCentralCrossRefPubMed Debiec H, Christensen EI, Ronco PM: The cell adhesion molecule L1 is developmentally regulated in the renal epithelium and is involved in kidney branching morphogenesis. J Cell Biol. 1998, 143: 2067-2079. 10.1083/jcb.143.7.2067.PubMedCentralCrossRefPubMed
12.
go back to reference Thor G, Probstmeier R, Schachner M: Characterization of the cell adhesion molecules L1, N-CAM and J1 in the mouse intestine. EMBO J. 1987, 6: 2581-2586.PubMedCentralPubMed Thor G, Probstmeier R, Schachner M: Characterization of the cell adhesion molecules L1, N-CAM and J1 in the mouse intestine. EMBO J. 1987, 6: 2581-2586.PubMedCentralPubMed
13.
go back to reference Ebeling O, Duczmal A, Aigner S, Geiger C, Schollhammer S, Kemshead JT, Moller P, Schwartz-Albiez R, Altevogt P: L1 adhesion molecule on human lymphocytes and monocytes: expression and involvement in binding to alpha v beta 3 integrin. Eur J Immunol. 1996, 26: 2508-2516. 10.1002/eji.1830261035.CrossRefPubMed Ebeling O, Duczmal A, Aigner S, Geiger C, Schollhammer S, Kemshead JT, Moller P, Schwartz-Albiez R, Altevogt P: L1 adhesion molecule on human lymphocytes and monocytes: expression and involvement in binding to alpha v beta 3 integrin. Eur J Immunol. 1996, 26: 2508-2516. 10.1002/eji.1830261035.CrossRefPubMed
14.
go back to reference Kajiwara Y, Ueno H, Hashiguchi Y, Shinto E, Shimazaki H, Mochizuki H, Hase K: Expression of l1 cell adhesion molecule and morphologic features at the invasive front of colorectal cancer. Am J Clin Pathol. 2011, 136: 138-144. 10.1309/AJCP63NRBNGCTXVF.CrossRefPubMed Kajiwara Y, Ueno H, Hashiguchi Y, Shinto E, Shimazaki H, Mochizuki H, Hase K: Expression of l1 cell adhesion molecule and morphologic features at the invasive front of colorectal cancer. Am J Clin Pathol. 2011, 136: 138-144. 10.1309/AJCP63NRBNGCTXVF.CrossRefPubMed
15.
go back to reference Doberstein K, Pfeilschifter J, Gutwein P: The transcription factor PAX2 regulates ADAM10 expression in renal cell carcinoma. Carcinogenesis. 2011, 32: 1713-1723. 10.1093/carcin/bgr195.CrossRefPubMed Doberstein K, Pfeilschifter J, Gutwein P: The transcription factor PAX2 regulates ADAM10 expression in renal cell carcinoma. Carcinogenesis. 2011, 32: 1713-1723. 10.1093/carcin/bgr195.CrossRefPubMed
16.
go back to reference Bondong S, Kiefel H, Hielscher T, Zeimet AG, Zeillinger R, Pils D, Schuster E, Castillo-Tong DC, Cadron I, Vergote I: Prognostic significance of L1CAM in ovarian cancer and its role in constitutive NF-kappaB activation. Ann Oncol. 2012, 23: 1795-1802. 10.1093/annonc/mdr568.CrossRefPubMed Bondong S, Kiefel H, Hielscher T, Zeimet AG, Zeillinger R, Pils D, Schuster E, Castillo-Tong DC, Cadron I, Vergote I: Prognostic significance of L1CAM in ovarian cancer and its role in constitutive NF-kappaB activation. Ann Oncol. 2012, 23: 1795-1802. 10.1093/annonc/mdr568.CrossRefPubMed
17.
go back to reference Kim KS, Min JK, Liang ZL, Lee K, Lee JU, Bae KH, Lee MH, Lee SE, Ryu MJ, Kim SJ: Aberrant l1 cell adhesion molecule affects tumor behavior and chemosensitivity in anaplastic thyroid carcinoma. Clin Cancer Res. 2012, 18: 3071-3078. 10.1158/1078-0432.CCR-11-2757.CrossRefPubMed Kim KS, Min JK, Liang ZL, Lee K, Lee JU, Bae KH, Lee MH, Lee SE, Ryu MJ, Kim SJ: Aberrant l1 cell adhesion molecule affects tumor behavior and chemosensitivity in anaplastic thyroid carcinoma. Clin Cancer Res. 2012, 18: 3071-3078. 10.1158/1078-0432.CCR-11-2757.CrossRefPubMed
18.
go back to reference Izumoto S, Ohnishi T, Arita N, Hiraga S, Taki T, Hayakawa T: Gene expression of neural cell adhesion molecule L1 in malignant gliomas and biological significance of L1 in glioma invasion. Cancer Res. 1996, 56: 1440-1444.PubMed Izumoto S, Ohnishi T, Arita N, Hiraga S, Taki T, Hayakawa T: Gene expression of neural cell adhesion molecule L1 in malignant gliomas and biological significance of L1 in glioma invasion. Cancer Res. 1996, 56: 1440-1444.PubMed
19.
go back to reference Hoefnagel CA, Rutgers M, Buitenhuis CK, Smets LA, de Kraker J, Meli M, Carrel F, Amstutz H, Schubiger PA, Novak-Hofer I: A comparison of targeting of neuroblastoma with mIBG and anti L1-CAM antibody mAb chCE7: therapeutic efficacy in a neuroblastoma xenograft model and imaging of neuroblastoma patients. Eur J Nucl Med. 2001, 28: 359-368. 10.1007/s002590000454.CrossRef Hoefnagel CA, Rutgers M, Buitenhuis CK, Smets LA, de Kraker J, Meli M, Carrel F, Amstutz H, Schubiger PA, Novak-Hofer I: A comparison of targeting of neuroblastoma with mIBG and anti L1-CAM antibody mAb chCE7: therapeutic efficacy in a neuroblastoma xenograft model and imaging of neuroblastoma patients. Eur J Nucl Med. 2001, 28: 359-368. 10.1007/s002590000454.CrossRef
20.
go back to reference Thies A, Schachner M, Moll I, Berger J, Schulze HJ, Brunner G, Schumacher U: Overexpression of the cell adhesion molecule L1 is associated with metastasis in cutaneous malignant melanoma. Eur J Cancer. 2002, 38: 1708-1716. 10.1016/S0959-8049(02)00105-3.CrossRefPubMed Thies A, Schachner M, Moll I, Berger J, Schulze HJ, Brunner G, Schumacher U: Overexpression of the cell adhesion molecule L1 is associated with metastasis in cutaneous malignant melanoma. Eur J Cancer. 2002, 38: 1708-1716. 10.1016/S0959-8049(02)00105-3.CrossRefPubMed
21.
go back to reference Haspel J, Grumet M: The L1CAM extracellular region: a multi-domain protein with modular and cooperative binding modes. Front Biosci. 2003, 8: s1210-s1225. 10.2741/1108.CrossRefPubMed Haspel J, Grumet M: The L1CAM extracellular region: a multi-domain protein with modular and cooperative binding modes. Front Biosci. 2003, 8: s1210-s1225. 10.2741/1108.CrossRefPubMed
22.
go back to reference Voura EB, Ramjeesingh RA, Montgomery AM, Siu CH: Involvement of integrin alpha(v)beta(3) and cell adhesion molecule L1 in transendothelial migration of melanoma cells. Mol Biol Cell. 2001, 12: 2699-2710. 10.1091/mbc.12.9.2699.PubMedCentralCrossRefPubMed Voura EB, Ramjeesingh RA, Montgomery AM, Siu CH: Involvement of integrin alpha(v)beta(3) and cell adhesion molecule L1 in transendothelial migration of melanoma cells. Mol Biol Cell. 2001, 12: 2699-2710. 10.1091/mbc.12.9.2699.PubMedCentralCrossRefPubMed
23.
go back to reference Duczmal A, Schollhammer S, Katich S, Ebeling O, Schwartz-Albiez R, Altevogt P: The L1 adhesion molecule supports alpha v beta 3-mediated migration of human tumor cells and activated T lymphocytes. Biochem Biophys Res Commun. 1997, 232: 236-239. 10.1006/bbrc.1997.6265.CrossRefPubMed Duczmal A, Schollhammer S, Katich S, Ebeling O, Schwartz-Albiez R, Altevogt P: The L1 adhesion molecule supports alpha v beta 3-mediated migration of human tumor cells and activated T lymphocytes. Biochem Biophys Res Commun. 1997, 232: 236-239. 10.1006/bbrc.1997.6265.CrossRefPubMed
24.
go back to reference Gavert N, Vivanti A, Hazin J, Brabletz T, Ben-Ze’ev A: L1-mediated colon cancer cell metastasis does not require changes in EMT and cancer stem cell markers. Mol Cancer Res. 2011, 9: 14-24. 10.1158/1541-7786.MCR-10-0406.CrossRefPubMed Gavert N, Vivanti A, Hazin J, Brabletz T, Ben-Ze’ev A: L1-mediated colon cancer cell metastasis does not require changes in EMT and cancer stem cell markers. Mol Cancer Res. 2011, 9: 14-24. 10.1158/1541-7786.MCR-10-0406.CrossRefPubMed
25.
go back to reference Min JK, Kim JM, Li S, Lee JW, Yoon H, Ryu CJ, Jeon SH, Lee JH, Kim JY, Yoon HK: L1 cell adhesion molecule is a novel therapeutic target in intrahepatic cholangiocarcinoma. Clin Cancer Res. 2010, 16: 3571-3580. 10.1158/1078-0432.CCR-09-3075.CrossRefPubMed Min JK, Kim JM, Li S, Lee JW, Yoon H, Ryu CJ, Jeon SH, Lee JH, Kim JY, Yoon HK: L1 cell adhesion molecule is a novel therapeutic target in intrahepatic cholangiocarcinoma. Clin Cancer Res. 2010, 16: 3571-3580. 10.1158/1078-0432.CCR-09-3075.CrossRefPubMed
26.
go back to reference Jung J, Son YS, Park H, Jeon SK, Lee JW, Choi SY, Kim JM, Kwon YG, Hong HJ, Min JK: The cell adhesion molecule L1 promotes gallbladder carcinoma progression in vitro and in vivo. Oncol Rep. 2011, 25: 945-952.PubMed Jung J, Son YS, Park H, Jeon SK, Lee JW, Choi SY, Kim JM, Kwon YG, Hong HJ, Min JK: The cell adhesion molecule L1 promotes gallbladder carcinoma progression in vitro and in vivo. Oncol Rep. 2011, 25: 945-952.PubMed
27.
go back to reference Kodera Y, Nakanishi H, Ito S, Misawa K, Ito Y, Nakayama G, Koike M, Fujiwara M, Yamamura Y, Nakao A: Expression of L1 cell adhesion molecule is a significant prognostic factor in pT3-stage gastric cancer. Anticancer Res. 2009, 29: 4033-4039.PubMed Kodera Y, Nakanishi H, Ito S, Misawa K, Ito Y, Nakayama G, Koike M, Fujiwara M, Yamamura Y, Nakao A: Expression of L1 cell adhesion molecule is a significant prognostic factor in pT3-stage gastric cancer. Anticancer Res. 2009, 29: 4033-4039.PubMed
28.
go back to reference Datta SR, Brunet A, Greenberg ME: Cellular survival: a play in three Akts. Genes Dev. 1999, 13: 2905-2927. 10.1101/gad.13.22.2905.CrossRefPubMed Datta SR, Brunet A, Greenberg ME: Cellular survival: a play in three Akts. Genes Dev. 1999, 13: 2905-2927. 10.1101/gad.13.22.2905.CrossRefPubMed
29.
go back to reference Scheid MP, Woodgett JR: PKB/AKT: functional insights from genetic models. Nat Rev Mol Cell Biol. 2001, 2: 760-768. 10.1038/35096067.CrossRefPubMed Scheid MP, Woodgett JR: PKB/AKT: functional insights from genetic models. Nat Rev Mol Cell Biol. 2001, 2: 760-768. 10.1038/35096067.CrossRefPubMed
31.
go back to reference Fogel M, Gutwein P, Mechtersheimer S, Riedle S, Stoeck A, Smirnov A, Edler L, Ben-Arie A, Huszar M, Altevogt P: L1 expression as a predictor of progression and survival in patients with uterine and ovarian carcinomas. Lancet. 2003, 362: 869-875. 10.1016/S0140-6736(03)14342-5.CrossRefPubMed Fogel M, Gutwein P, Mechtersheimer S, Riedle S, Stoeck A, Smirnov A, Edler L, Ben-Arie A, Huszar M, Altevogt P: L1 expression as a predictor of progression and survival in patients with uterine and ovarian carcinomas. Lancet. 2003, 362: 869-875. 10.1016/S0140-6736(03)14342-5.CrossRefPubMed
32.
go back to reference Fogel M, Mechtersheimer S, Huszar M, Smirnov A, Abu-Dahi A, Tilgen W, Reichrath J, Georg T, Altevogt P, Gutwein P: L1 adhesion molecule (CD 171) in development and progression of human malignant melanoma. Cancer Lett. 2003, 189: 237-247. 10.1016/S0304-3835(02)00513-X.CrossRefPubMed Fogel M, Mechtersheimer S, Huszar M, Smirnov A, Abu-Dahi A, Tilgen W, Reichrath J, Georg T, Altevogt P, Gutwein P: L1 adhesion molecule (CD 171) in development and progression of human malignant melanoma. Cancer Lett. 2003, 189: 237-247. 10.1016/S0304-3835(02)00513-X.CrossRefPubMed
33.
go back to reference Ohnishi T, Matsumura H, Izumoto S, Hiraga S, Hayakawa T: A novel model of glioma cell invasion using organotypic brain slice culture. Cancer Res. 1998, 58: 2935-2940.PubMed Ohnishi T, Matsumura H, Izumoto S, Hiraga S, Hayakawa T: A novel model of glioma cell invasion using organotypic brain slice culture. Cancer Res. 1998, 58: 2935-2940.PubMed
34.
go back to reference Boo YJ, Park JM, Kim J, Chae YS, Min BW, Um JW, Moon HY: L1 expression as a marker for poor prognosis, tumor progression, and short survival in patients with colorectal cancer. Ann Surg Oncol. 2007, 14: 1703-1711. 10.1245/s10434-006-9281-8.CrossRefPubMed Boo YJ, Park JM, Kim J, Chae YS, Min BW, Um JW, Moon HY: L1 expression as a marker for poor prognosis, tumor progression, and short survival in patients with colorectal cancer. Ann Surg Oncol. 2007, 14: 1703-1711. 10.1245/s10434-006-9281-8.CrossRefPubMed
35.
go back to reference Kaifi JT, Reichelt U, Quaas A, Schurr PG, Wachowiak R, Yekebas EF, Strate T, Schneider C, Pantel K, Schachner M: L1 is associated with micrometastatic spread and poor outcome in colorectal cancer. Mod Pathol. 2007, 20: 1183-1190. 10.1038/modpathol.3800955.CrossRefPubMed Kaifi JT, Reichelt U, Quaas A, Schurr PG, Wachowiak R, Yekebas EF, Strate T, Schneider C, Pantel K, Schachner M: L1 is associated with micrometastatic spread and poor outcome in colorectal cancer. Mod Pathol. 2007, 20: 1183-1190. 10.1038/modpathol.3800955.CrossRefPubMed
36.
go back to reference Gavert N, Conacci-Sorrell M, Gast D, Schneider A, Altevogt P, Brabletz T, Ben-Ze'ev A: L1, a novel target of beta-catenin signaling, transforms cells and is expressed at the invasive front of colon cancers. J Cell Biol. 2005, 168: 633-642. 10.1083/jcb.200408051.PubMedCentralCrossRefPubMed Gavert N, Conacci-Sorrell M, Gast D, Schneider A, Altevogt P, Brabletz T, Ben-Ze'ev A: L1, a novel target of beta-catenin signaling, transforms cells and is expressed at the invasive front of colon cancers. J Cell Biol. 2005, 168: 633-642. 10.1083/jcb.200408051.PubMedCentralCrossRefPubMed
37.
38.
go back to reference Panicker AK, Buhusi M, Erickson A, Maness PF: Endocytosis of beta1 integrins is an early event in migration promoted by the cell adhesion molecule L1. Exp Cell Res. 2006, 312: 299-307.PubMed Panicker AK, Buhusi M, Erickson A, Maness PF: Endocytosis of beta1 integrins is an early event in migration promoted by the cell adhesion molecule L1. Exp Cell Res. 2006, 312: 299-307.PubMed
39.
go back to reference Yang M, Li Y, Chilukuri K, Brady OA, Boulos MI, Kappes JC, Galileo DS: L1 stimulation of human glioma cell motility correlates with FAK activation. J Neurooncol. 2011, 105: 27-44. 10.1007/s11060-011-0557-x.PubMedCentralCrossRefPubMed Yang M, Li Y, Chilukuri K, Brady OA, Boulos MI, Kappes JC, Galileo DS: L1 stimulation of human glioma cell motility correlates with FAK activation. J Neurooncol. 2011, 105: 27-44. 10.1007/s11060-011-0557-x.PubMedCentralCrossRefPubMed
40.
go back to reference Kiefel H, Bondong S, Pfeifer M, Schirmer U, Erbe-Hoffmann N, Schafer H, Sebens S, Altevogt P: EMT-associated up-regulation of L1CAM provides insights into L1CAM-mediated integrin signalling and NF-kappaB activation. Carcinogenesis. 2012, 33: 1919-1929. 10.1093/carcin/bgs220.CrossRefPubMed Kiefel H, Bondong S, Pfeifer M, Schirmer U, Erbe-Hoffmann N, Schafer H, Sebens S, Altevogt P: EMT-associated up-regulation of L1CAM provides insights into L1CAM-mediated integrin signalling and NF-kappaB activation. Carcinogenesis. 2012, 33: 1919-1929. 10.1093/carcin/bgs220.CrossRefPubMed
41.
go back to reference Kiefel H, Bondong S, Erbe-Hoffmann N, Hazin J, Riedle S, Wolf J, Pfeifer M, Arlt A, Schafer H, Muerkoster SS, Altevogt P: L1CAM-integrin interaction induces constitutive NF-kappaB activation in pancreatic adenocarcinoma cells by enhancing IL-1beta expression. Oncogene. 2010, 29: 4766-4778. 10.1038/onc.2010.230.CrossRefPubMed Kiefel H, Bondong S, Erbe-Hoffmann N, Hazin J, Riedle S, Wolf J, Pfeifer M, Arlt A, Schafer H, Muerkoster SS, Altevogt P: L1CAM-integrin interaction induces constitutive NF-kappaB activation in pancreatic adenocarcinoma cells by enhancing IL-1beta expression. Oncogene. 2010, 29: 4766-4778. 10.1038/onc.2010.230.CrossRefPubMed
42.
go back to reference Bao S, Wu Q, Li Z, Sathornsumetee S, Wang H, McLendon RE, Hjelmeland AB, Rich JN: Targeting cancer stem cells through L1CAM suppresses glioma growth. Cancer Res. 2008, 68: 6043-6048. 10.1158/0008-5472.CAN-08-1079.PubMedCentralCrossRefPubMed Bao S, Wu Q, Li Z, Sathornsumetee S, Wang H, McLendon RE, Hjelmeland AB, Rich JN: Targeting cancer stem cells through L1CAM suppresses glioma growth. Cancer Res. 2008, 68: 6043-6048. 10.1158/0008-5472.CAN-08-1079.PubMedCentralCrossRefPubMed
43.
go back to reference Gast D, Riedle S, Issa Y, Pfeifer M, Beckhove P, Sanderson MP, Arlt M, Moldenhauer G, Fogel M, Kruger A, Altevogt P: The cytoplasmic part of L1-CAM controls growth and gene expression in human tumors that is reversed by therapeutic antibodies. Oncogene. 2008, 27: 1281-1289. 10.1038/sj.onc.1210747.CrossRefPubMed Gast D, Riedle S, Issa Y, Pfeifer M, Beckhove P, Sanderson MP, Arlt M, Moldenhauer G, Fogel M, Kruger A, Altevogt P: The cytoplasmic part of L1-CAM controls growth and gene expression in human tumors that is reversed by therapeutic antibodies. Oncogene. 2008, 27: 1281-1289. 10.1038/sj.onc.1210747.CrossRefPubMed
44.
go back to reference Arlt MJ, Novak-Hofer I, Gast D, Gschwend V, Moldenhauer G, Grunberg J, Honer M, Schubiger PA, Altevogt P, Kruger A: Efficient inhibition of intra-peritoneal tumor growth and dissemination of human ovarian carcinoma cells in nude mice by anti-L1-cell adhesion molecule monoclonal antibody treatment. Cancer Res. 2006, 66: 936-943. 10.1158/0008-5472.CAN-05-1818.CrossRefPubMed Arlt MJ, Novak-Hofer I, Gast D, Gschwend V, Moldenhauer G, Grunberg J, Honer M, Schubiger PA, Altevogt P, Kruger A: Efficient inhibition of intra-peritoneal tumor growth and dissemination of human ovarian carcinoma cells in nude mice by anti-L1-cell adhesion molecule monoclonal antibody treatment. Cancer Res. 2006, 66: 936-943. 10.1158/0008-5472.CAN-05-1818.CrossRefPubMed
45.
go back to reference Knogler K, Grunberg J, Zimmermann K, Cohrs S, Honer M, Ametamey S, Altevogt P, Fogel M, Schubiger PA, Novak-Hofer I: Copper-67 radioimmunotherapy and growth inhibition by anti-L1-cell adhesion molecule monoclonal antibodies in a therapy model of ovarian cancer metastasis. Clin Cancer Res. 2007, 13: 603-611. 10.1158/1078-0432.CCR-06-1486.CrossRefPubMed Knogler K, Grunberg J, Zimmermann K, Cohrs S, Honer M, Ametamey S, Altevogt P, Fogel M, Schubiger PA, Novak-Hofer I: Copper-67 radioimmunotherapy and growth inhibition by anti-L1-cell adhesion molecule monoclonal antibodies in a therapy model of ovarian cancer metastasis. Clin Cancer Res. 2007, 13: 603-611. 10.1158/1078-0432.CCR-06-1486.CrossRefPubMed
46.
go back to reference Sebens Muerkoster S, Werbing V, Sipos B, Debus MA, Witt M, Grossmann M, Leisner D, Kotteritzsch J, Kappes H, Kloppel G: Drug-induced expression of the cellular adhesion molecule L1CAM confers anti-apoptotic protection and chemoresistance in pancreatic ductal adenocarcinoma cells. Oncogene. 2007, 26: 2759-2768. 10.1038/sj.onc.1210076.CrossRefPubMed Sebens Muerkoster S, Werbing V, Sipos B, Debus MA, Witt M, Grossmann M, Leisner D, Kotteritzsch J, Kappes H, Kloppel G: Drug-induced expression of the cellular adhesion molecule L1CAM confers anti-apoptotic protection and chemoresistance in pancreatic ductal adenocarcinoma cells. Oncogene. 2007, 26: 2759-2768. 10.1038/sj.onc.1210076.CrossRefPubMed
47.
go back to reference Schafer H, Dieckmann C, Korniienko O, Moldenhauer G, Kiefel H, Salnikov A, Kruger A, Altevogt P, Sebens S: Combined treatment of L1CAM antibodies and cytostatic drugs improve the therapeutic response of pancreatic and ovarian carcinoma. Cancer Lett. 2012, 319: 66-82. 10.1016/j.canlet.2011.12.035.CrossRefPubMed Schafer H, Dieckmann C, Korniienko O, Moldenhauer G, Kiefel H, Salnikov A, Kruger A, Altevogt P, Sebens S: Combined treatment of L1CAM antibodies and cytostatic drugs improve the therapeutic response of pancreatic and ovarian carcinoma. Cancer Lett. 2012, 319: 66-82. 10.1016/j.canlet.2011.12.035.CrossRefPubMed
48.
go back to reference Silletti S, Yebra M, Perez B, Cirulli V, McMahon M, Montgomery AM: Extracellular signal-regulated kinase (ERK)-dependent gene expression contributes to L1 cell adhesion molecule-dependent motility and invasion. J Biol Chem. 2004, 279: 28880-28888. 10.1074/jbc.M404075200.CrossRefPubMed Silletti S, Yebra M, Perez B, Cirulli V, McMahon M, Montgomery AM: Extracellular signal-regulated kinase (ERK)-dependent gene expression contributes to L1 cell adhesion molecule-dependent motility and invasion. J Biol Chem. 2004, 279: 28880-28888. 10.1074/jbc.M404075200.CrossRefPubMed
49.
go back to reference Stoeck A, Gast D, Sanderson MP, Issa Y, Gutwein P, Altevogt P: L1-CAM in a membrane-bound or soluble form augments protection from apoptosis in ovarian carcinoma cells. Gynecol Oncol. 2007, 104: 461-469. 10.1016/j.ygyno.2006.08.038.CrossRefPubMed Stoeck A, Gast D, Sanderson MP, Issa Y, Gutwein P, Altevogt P: L1-CAM in a membrane-bound or soluble form augments protection from apoptosis in ovarian carcinoma cells. Gynecol Oncol. 2007, 104: 461-469. 10.1016/j.ygyno.2006.08.038.CrossRefPubMed
50.
go back to reference Yoon H, Min JK, Lee DG, Kim DG, Koh SS, Hong HJ: L1 cell adhesion molecule and epidermal growth factor receptor activation confer cisplatin resistance in intrahepatic cholangiocarcinoma cells. Cancer Lett. 2012, 316: 70-76. 10.1016/j.canlet.2011.10.024.CrossRefPubMed Yoon H, Min JK, Lee DG, Kim DG, Koh SS, Hong HJ: L1 cell adhesion molecule and epidermal growth factor receptor activation confer cisplatin resistance in intrahepatic cholangiocarcinoma cells. Cancer Lett. 2012, 316: 70-76. 10.1016/j.canlet.2011.10.024.CrossRefPubMed
51.
go back to reference Zeng ZL, Wu WJ, Yang J, Tang ZJ, Chen DL, Qiu MZ, Luo HY, Wang ZQ, Jin Y, Wang DS, Xu RH: Prognostic relevance of melanoma antigen D1 expression in colorectal carcinoma. J Transl Med. 2012, 10: 181-10.1186/1479-5876-10-181.PubMedCentralCrossRefPubMed Zeng ZL, Wu WJ, Yang J, Tang ZJ, Chen DL, Qiu MZ, Luo HY, Wang ZQ, Jin Y, Wang DS, Xu RH: Prognostic relevance of melanoma antigen D1 expression in colorectal carcinoma. J Transl Med. 2012, 10: 181-10.1186/1479-5876-10-181.PubMedCentralCrossRefPubMed
52.
go back to reference Zou J, Li P, Lu F, Liu N, Dai J, Ye J, Qu X, Sun X, Ma D, Park J, Ji C: Notch1 is required for hypoxia-induced proliferation, invasion and chemoresistance of T-cell acute lymphoblastic leukemia cells. J Hematol Oncol. 2013, 6: 3-10.1186/1756-8722-6-3.PubMedCentralCrossRefPubMed Zou J, Li P, Lu F, Liu N, Dai J, Ye J, Qu X, Sun X, Ma D, Park J, Ji C: Notch1 is required for hypoxia-induced proliferation, invasion and chemoresistance of T-cell acute lymphoblastic leukemia cells. J Hematol Oncol. 2013, 6: 3-10.1186/1756-8722-6-3.PubMedCentralCrossRefPubMed
53.
go back to reference Wu ZL, Song YQ, Shi YF, Zhu J: High nuclear expression of STAT3 is associated with unfavorable prognosis in diffuse large B-cell lymphoma. J Hematol Oncol. 2011, 4: 31-10.1186/1756-8722-4-31.CrossRefPubMed Wu ZL, Song YQ, Shi YF, Zhu J: High nuclear expression of STAT3 is associated with unfavorable prognosis in diffuse large B-cell lymphoma. J Hematol Oncol. 2011, 4: 31-10.1186/1756-8722-4-31.CrossRefPubMed
54.
go back to reference Lee SB, Schramme A, Doberstein K, Dummer R, Abdel-Bakky MS, Keller S, Altevogt P, Oh ST, Reichrath J, Oxmann D: ADAM10 is upregulated in melanoma metastasis compared with primary melanoma. J Invest Dermatol. 2010, 130: 763-773. 10.1038/jid.2009.335.CrossRefPubMed Lee SB, Schramme A, Doberstein K, Dummer R, Abdel-Bakky MS, Keller S, Altevogt P, Oh ST, Reichrath J, Oxmann D: ADAM10 is upregulated in melanoma metastasis compared with primary melanoma. J Invest Dermatol. 2010, 130: 763-773. 10.1038/jid.2009.335.CrossRefPubMed
55.
go back to reference Huang S, Jean D, Luca M, Tainsky MA, Bar-Eli M: Loss of AP-2 results in downregulation of c-KIT and enhancement of melanoma tumorigenicity and metastasis. EMBO J. 1998, 17: 4358-4369. 10.1093/emboj/17.15.4358.PubMedCentralCrossRefPubMed Huang S, Jean D, Luca M, Tainsky MA, Bar-Eli M: Loss of AP-2 results in downregulation of c-KIT and enhancement of melanoma tumorigenicity and metastasis. EMBO J. 1998, 17: 4358-4369. 10.1093/emboj/17.15.4358.PubMedCentralCrossRefPubMed
Metadata
Title
L1cam promotes tumor progression and metastasis and is an independent unfavorable prognostic factor in gastric cancer
Authors
Dong-liang Chen
Zhao-lei Zeng
Jing Yang
Chao Ren
De-shen Wang
Wen-jing Wu
Rui-hua Xu
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2013
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/1756-8722-6-43

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