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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 13/2012

01-12-2012 | Translational Research and Biomarkers

Low Expression of Junctional Adhesion Molecule A Is Associated with Metastasis and Poor Survival in Pancreatic Cancer

Authors: Dominic Fong, MD, Gilbert Spizzo, MD, Manfred Mitterer, MD, Andreas Seeber, MD, Michael Steurer, MD, Guenther Gastl, MD, Ines Brosch, Patrizia Moser, MD

Published in: Annals of Surgical Oncology | Issue 13/2012

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Abstract

Background

Characterized by its highly aggressive tumor biology, pancreatic cancer still remains a fatal diagnosis. The junctional adhesion molecule A (JAM-A) is a type I transmembrane glycoprotein, which recently has been shown to affect the prognosis of several human malignancies.

Methods

JAM-A antigen expression was investigated retrospectively by immunohistochemistry in paraffin-embedded primary tumor tissue samples from a series (n = 186) of consecutive patients with pancreatic adenocarcinoma. Survival was calculated by Kaplan–Meier curves. Parameters found to be of prognostic significance in univariate analysis were verified in a multivariate Cox regression model.

Results

Low expression of JAM-A was observed in 79 (42 %) of 186 pancreatic cancer specimens and was significantly associated with poor overall survival (P < 0.01). By univariate analysis, low expression of JAM-A was found to correlate with positive lymph node status (P = 0.02), the presence of distant metastasis (P = 0.05), and tumor grade (P = 0.04), suggesting it may be an important event involved in cancer progression. Furthermore, in the subgroup of patients with surgically resected pancreatic cancer, low expression of JAM-A significantly correlated with decreased progression-free survival (P < 0.01). Multivariate analysis revealed JAM-A to be an independent predictor of poor outcome.

Discussion

These findings suggest for the first time that low levels of JAM-A expression in pancreatic cancer are associated with poor clinical outcome. JAM-A may represents a target molecule for functional inactivation and serve as a novel biomarker of adverse prognosis in pancreatic cancer.
Literature
1.
2.
Cameron JL, Riall TS, Coleman J, Belcher KA. One thousand consecutive pancreaticoduodenectomies. Ann Surg. 2006;244:10–5.PubMedCrossRef
3.
Wagner M, Redaelli C, Lietz M, Seiler CA, Friess H, Buchler MW. Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinoma. Br J Surg. 2004;91:586–94.PubMedCrossRef
4.
Moore MJ, Goldstein D, Hamm J, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007;25:1960–6.PubMedCrossRef
5.
Martin-Padura I, Lostaglio S, Schneemann M, et al. Junctional adhesion molecule, a novel member of the immunoglobulin superfamily that distributes at intercellular junctions and modulates monocyte transmigration. J Cell Biol. 1998;142:117–27.PubMedCrossRef
6.
Naik UP, Eckfeld K. Junctional adhesion molecule 1 (JAM-1). J Biol Regul Homeost Agents. 2003;17:341–7.PubMed
7.
8.
Liu Y, Nusrat A, Schnell FJ, et al. Human junction adhesion molecule regulates tight junction resealing in epithelia. J Cell Sci. 2000;113(Pt 13):2363–74.PubMed
9.
Liang TW, DeMarco RA, Mrsny RJ, et al. Characterization of huJAM: evidence for involvement in cell–cell contact and tight junction regulation. Am J Physiol Cell Physiol. 2000;279:C1733–43.PubMed
10.
Del Maschio A, De Luigi A, Martin-Padura I, et al. Leukocyte recruitment in the cerebrospinal fluid of mice with experimental meningitis is inhibited by an antibody to junctional adhesion molecule (JAM). J Exp Med. 1999;190:1351–6.PubMedCrossRef
11.
Sobocka MB, Sobocki T, Banerjee P, et al. Cloning of the human platelet F11 receptor: a cell adhesion molecule member of the immunoglobulin superfamily involved in platelet aggregation. Blood. 2000;95:2600–9.PubMed
12.
Naik MU, Mousa SA, Parkos CA, Naik UP. Signaling through JAM-1 and alphavbeta3 is required for the angiogenic action of bFGF: dissociation of the JAM-1 and alphavbeta3 complex. Blood. 2003;102:2108–14.PubMedCrossRef
13.
Kornecki E, Walkowiak B, Naik UP, Ehrlich YH. Activation of human platelets by a stimulatory monoclonal antibody. J Biol Chem. 1990;265:10042–8.PubMed
14.
Aurrand-Lions M, Duncan L, Ballestrem C, Imhof BA. JAM-2, a novel immunoglobulin superfamily molecule, expressed by endothelial and lymphatic cells. J Biol Chem. 2001;276:2733–41.PubMedCrossRef
15.
Gupta SK, Pillarisetti K, Ohlstein EH. Platelet agonist F11 receptor is a member of the immunoglobulin superfamily and identical with junctional adhesion molecule (JAM): regulation of expression in human endothelial cells and macrophages. IUBMB Life. 2000;50:51–6.PubMedCrossRef
16.
Yamaguchi H, Kojima T, Ito T, et al. Transcriptional control of tight junction proteins via a protein kinase C signal pathway in human telomerase reverse transcriptase–transfected human pancreatic duct epithelial cells. Am J Pathol. 2010;177:698–712.PubMedCrossRef
17.
Williams LA, Martin-Padura I, Dejana E, Hogg N, Simmons DL. Identification and characterisation of human junctional adhesion molecule (JAM). Mol Immunol. 1999;36:1175–88.PubMedCrossRef
18.
McSherry EA, McGee SF, Jirstrom K, et al. JAM-A expression positively correlates with poor prognosis in breast cancer patients. Int J Cancer. 2009;125:1343–51.PubMedCrossRef
19.
Naik MU, Naik TU, Suckow AT, Duncan MK, Naik UP. Attenuation of junctional adhesion molecule-A is a contributing factor for breast cancer cell invasion. Cancer Res. 2008;68:2194–203.PubMedCrossRef
20.
Gutwein P, Schramme A, Voss B, et al. Downregulation of junctional adhesion molecule-A is involved in the progression of clear cell renal cell carcinoma. Biochem Biophys Res Commun. 2009;380:387–91.PubMedCrossRef
21.
Chlenski A, Ketels KV, Tsao MS, et al. Tight junction protein ZO-2 is differentially expressed in normal pancreatic ducts compared to human pancreatic adenocarcinoma. Int J Cancer. 1999;82:137–44.PubMedCrossRef
22.
Sobin LH, Fleming ID. TNM classification of malignant tumors, fifth edition (1997). Union Internationale Contre le Cancer and the American Joint Committee on Cancer. Cancer. 1997;80:1803–4.
23.
Martin TA, Jiang WG. Loss of tight junction barrier function and its role in cancer metastasis. Biochim Biophys Acta. 2009;1788:872–91.PubMedCrossRef
24.
Shin K, Fogg VC, Margolis B. Tight junctions and cell polarity. Annu Rev Cell Dev Biol. 2006;22:207–35.PubMedCrossRef
25.
Lampugnani MG, Dejana E. Interendothelial junctions: structure, signalling and functional roles. Curr Opin Cell Biol. 1997;9:674–82.PubMedCrossRef
26.
Mandell KJ, Babbin BA, Nusrat A, Parkos CA. Junctional adhesion molecule 1 regulates epithelial cell morphology through effects on beta1 integrins and Rap1 activity. J Biol Chem. 2005;280:11665–74.PubMedCrossRef
27.
Balda MS, Matter K. Transmembrane proteins of tight junctions. Semin Cell Dev Biol. 2000;11:281–9.PubMedCrossRef
28.
Dejana E, Corada M, Lampugnani MG. Endothelial cell-to-cell junctions. FASEB J. 1995;9:910–8.PubMed
29.
Matter K, Balda MS. Biogenesis of tight junctions: the C-terminal domain of occludin mediates basolateral targeting. J Cell Sci. 1998;111(Pt 4):511–9.PubMed
30.
Tan X, Egami H, Ishikawa S, et al. Arrangement of expression and distribution of tight junction protein claudin-1 in cell dissociation of pancreatic cancer cells. Int J Oncol. 2004;25:1567–74.PubMed
31.
Borka K, Kaliszky P, Szabo E, et al. Claudin expression in pancreatic endocrine tumors as compared with ductal adenocarcinomas. Virchows Arch. 2007;450:549–57.PubMedCrossRef
32.
Takai E, Tan X, Tamori Y, Hirota M, Egami H, Ogawa M. Correlation of translocation of tight junction protein Zonula occludens-1 and activation of epidermal growth factor receptor in the regulation of invasion of pancreatic cancer cells. Int J Oncol. 2005;27:645–51.PubMed
33.
Michl P, Barth C, Buchholz M, et al. Claudin-4 expression decreases invasiveness and metastatic potential of pancreatic cancer. Cancer Res. 2003;63:6265–71.PubMed
34.
35.
Laukoetter MG, Nava P, Lee WY, et al. JAM-A regulates permeability and inflammation in the intestine in vivo. J Exp Med. 2007;204:3067–76.PubMedCrossRef
36.
Ghislin S, Obino D, Middendorp S, Boggetto N, Alcaide-Loridan C, Deshayes F. Junctional adhesion molecules are required for melanoma cell lines transendothelial migration in vitro. Pigment Cell Melanoma Res. 2011;24:504–11.PubMedCrossRef
37.
Nava P, Capaldo CT, Koch S, et al. JAM-A regulates epithelial proliferation through Akt/beta-catenin signalling. EMBO Rep. 2011;12:314–20.PubMedCrossRef
38.
Amieva MR, Vogelmann R, Covacci A, Tompkins LS, Nelson WJ, Falkow S. Disruption of the epithelial apical–junctional complex by Helicobacter pylori CagA. Science. 2003;300:1430–4.PubMedCrossRef
39.
McSherry EA, Brennan K, Hudson L, Hill AD, Hopkins AM. Breast cancer cell migration is regulated through junctional adhesion molecule-A-mediated activation of Rap1 GTPase. Breast Cancer Res. 2011;13:R31.PubMedCrossRef
40.
Gotte M, Mohr C, Koo CY, et al. miR-145-dependent targeting of junctional adhesion molecule A and modulation of fascin expression are associated with reduced breast cancer cell motility and invasiveness. Oncogene. 2010;29:6569–80.PubMedCrossRef
41.
Martin TA, Watkins G, Mansel RE, Jiang WG. Loss of tight junction plaque molecules in breast cancer tissues is associated with a poor prognosis in patients with breast cancer. Eur J Cancer. 2004;40:2717–25.PubMedCrossRef
Metadata
Title
Low Expression of Junctional Adhesion Molecule A Is Associated with Metastasis and Poor Survival in Pancreatic Cancer
Authors
Dominic Fong, MD
Gilbert Spizzo, MD
Manfred Mitterer, MD
Andreas Seeber, MD
Michael Steurer, MD
Guenther Gastl, MD
Ines Brosch
Patrizia Moser, MD
Publication date
01-12-2012
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 13/2012
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-012-2381-8

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