Skip to main content
Erschienen in: Annals of Surgical Oncology 10/2010

01.10.2010 | Gastrointestinal Oncology

Overexpression of Endothelial Cell Specific Molecule-1 (ESM-1) in Gastric Cancer

verfasst von: Ni Liu, MD, Lian-hai Zhang, PhD, Hong Du, BS, Ying Hu, BS, Gui-guo Zhang, BS, Xiao-hong Wang, MD, Ji-you Li, PhD, Jia-fu Ji, MD

Erschienen in: Annals of Surgical Oncology | Ausgabe 10/2010

Einloggen, um Zugang zu erhalten

Abstract

Background

The endothelial cell-specific molecule-1 (ESM-1) gene is involved in various biological events. This study was designed to clarify its clinical significance and explore its biological behavior in gastric cancer (GC).

Methods

ESM-1 mRNA expression was evaluated by real-time PCR in GC (n = 34) and matched adjacent normal tissues (n = 14). The expression of ESM-1 protein was investigated by immunohistochemistry in GC (n = 159) and matched normal tissues (n = 40), and its correlation with the clinicopathological features and overall survival of patients was analyzed. Microvessel density (MVD) in GC was assessed by anti-CD34 and the pattern of ESM-1 expression in tumor-related vascular was evaluated. The effect of ESM-1 promotion of proliferation in the GC MKN28 cell line and human microvascular endothelial cell line HMEC-1 were tested using the MTT assay.

Results

ESM-1 mRNA was significantly overexpressed in GC compared with adjacent noncarcinoma controls (P < 0.01). ESM-1 protein was predominantly expressed in GC. ESM-1 expression was associated with distant metastasis and Borrmann type IV (P < 0.05) and was strongly associated with vascular invasion (P = 0.0057). Patients with ESM-1 expression showed lower 5-year survival rate (P = 0.0339). Multivariate analysis revealed that ESM-1 was an independent prognostic factor. In GC, CD34-MVD of GC vessels positively expressing ESM-1 was higher than that of GC with negative vessels expression of ESM-1 (P < 0.05). Besides, ESM-1 antibody dose-dependently impaired MKN28 and HMEC-1 growth.

Conclusions

ESM-1 is overexpressed in GC and can serve as a tumor biomarker to predict survival of GC patients, and it might promote tumor angiogenesis and growth in GC and, hence, may represent a potential therapeutic target.
Literatur
2.
Zurück zum Zitat Yang L. Incidence and mortality of gastric cancer in China. World J Gastroenterol. 2006;12:17–20.PubMed Yang L. Incidence and mortality of gastric cancer in China. World J Gastroenterol. 2006;12:17–20.PubMed
3.
Zurück zum Zitat Zirbes TK, Baldus SE, Moenig SP, et al. Tenascin expression in gastric cancer with special emphasis on the WHO-, Lauren-, and Goseki-classifications. Int J Mol Med. 1999;4:39–42.PubMed Zirbes TK, Baldus SE, Moenig SP, et al. Tenascin expression in gastric cancer with special emphasis on the WHO-, Lauren-, and Goseki-classifications. Int J Mol Med. 1999;4:39–42.PubMed
5.
Zurück zum Zitat Lassalle P, Molet S, Janin A, et al. ESM-1 is a novel human endothelial cell-specific molecule expressed in lung and regulated by cytokines. J Biol Chem. 1996;271:20458.CrossRef Lassalle P, Molet S, Janin A, et al. ESM-1 is a novel human endothelial cell-specific molecule expressed in lung and regulated by cytokines. J Biol Chem. 1996;271:20458.CrossRef
6.
Zurück zum Zitat Sarrazin S, Adam E, Lyon M, et al. Endocan or endothelial cell specific molecule-1 (ESM-1): a potential novel endothelial cell marker and a new target for cancer therapy. BBA Rev Cancer. 2006;1765:25–37. Sarrazin S, Adam E, Lyon M, et al. Endocan or endothelial cell specific molecule-1 (ESM-1): a potential novel endothelial cell marker and a new target for cancer therapy. BBA Rev Cancer. 2006;1765:25–37.
7.
Zurück zum Zitat Bechard D, Gentina T, Delehedde M, et al. Endocan is a novel chondroitin sulfate/dermatan sulfate proteoglycan that promotes hepatocyte growth factor/scatter factor mitogenic activity. J Biol Chem. 2001;276:48341–9. Bechard D, Gentina T, Delehedde M, et al. Endocan is a novel chondroitin sulfate/dermatan sulfate proteoglycan that promotes hepatocyte growth factor/scatter factor mitogenic activity. J Biol Chem. 2001;276:48341–9.
8.
Zurück zum Zitat Bechard D, Meignin V, Scherpereel A, et al. Characterization of the secreted form of endothelial-cell-specific molecule 1 by specific monoclonal antibodies. J Vasc Res. 2000;37:417–25.CrossRefPubMed Bechard D, Meignin V, Scherpereel A, et al. Characterization of the secreted form of endothelial-cell-specific molecule 1 by specific monoclonal antibodies. J Vasc Res. 2000;37:417–25.CrossRefPubMed
9.
Zurück zum Zitat Abid M, Yi X, Yano K, et al. Vascular endocan is preferentially expressed in tumor endothelium. Microvasc Res. 2006;72:136–45.CrossRefPubMed Abid M, Yi X, Yano K, et al. Vascular endocan is preferentially expressed in tumor endothelium. Microvasc Res. 2006;72:136–45.CrossRefPubMed
10.
Zurück zum Zitat Scherpereel A, Depontieu F, Grigoriu B, et al. Endocan, a new endothelial marker in human sepsis. Critical Care Med. 2006;34:532.CrossRef Scherpereel A, Depontieu F, Grigoriu B, et al. Endocan, a new endothelial marker in human sepsis. Critical Care Med. 2006;34:532.CrossRef
11.
Zurück zum Zitat Grigoriu B, Depontieu F, Scherpereel A, et al. Endocan expression and relationship with survival in human non-small cell lung cancer. Clin Cancer Res. 2006;12:4575–82.CrossRefPubMed Grigoriu B, Depontieu F, Scherpereel A, et al. Endocan expression and relationship with survival in human non-small cell lung cancer. Clin Cancer Res. 2006;12:4575–82.CrossRefPubMed
12.
Zurück zum Zitat Aitkenhead M, Wang S, Nakatsu M, et al. Identification of endothelial cell genes expressed in an in vitro model of angiogenesis: induction of ESM-1, βig-h3, and NrCAM. Microvasc Res. 2002;63:159–71.CrossRefPubMed Aitkenhead M, Wang S, Nakatsu M, et al. Identification of endothelial cell genes expressed in an in vitro model of angiogenesis: induction of ESM-1, βig-h3, and NrCAM. Microvasc Res. 2002;63:159–71.CrossRefPubMed
13.
Zurück zum Zitat Tanigawa N, Amaya H, Matsumura M, et al. Association between tumor angiogenesis and Borrmann type 4 carcinomas of the stomach. Oncology. 2000;55:461–7.CrossRef Tanigawa N, Amaya H, Matsumura M, et al. Association between tumor angiogenesis and Borrmann type 4 carcinomas of the stomach. Oncology. 2000;55:461–7.CrossRef
14.
Zurück zum Zitat Weidner N. Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors. Breast Cancer Res Treat. 1995;36:169–80.CrossRefPubMed Weidner N. Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors. Breast Cancer Res Treat. 1995;36:169–80.CrossRefPubMed
15.
Zurück zum Zitat Lenburg M, Liou L, Gerry N, et al. Previously unidentified changes in renal cell carcinoma gene expression identified by parametric analysis of microarray data. BMC Cancer. 2003;3:31.CrossRefPubMed Lenburg M, Liou L, Gerry N, et al. Previously unidentified changes in renal cell carcinoma gene expression identified by parametric analysis of microarray data. BMC Cancer. 2003;3:31.CrossRefPubMed
16.
Zurück zum Zitat van’t Veer L, Dai H, van de Vijver M, et al. Expression profiling predicts outcome in breast cancer. Breast Cancer Res. 2002;5:57.CrossRef van’t Veer L, Dai H, van de Vijver M, et al. Expression profiling predicts outcome in breast cancer. Breast Cancer Res. 2002;5:57.CrossRef
17.
Zurück zum Zitat Borczuk A, Shah L, Pearson G, et al. Molecular signatures in biopsy specimens of lung cancer. Am J Respir Crit Care Med. 2004;170:167.CrossRef Borczuk A, Shah L, Pearson G, et al. Molecular signatures in biopsy specimens of lung cancer. Am J Respir Crit Care Med. 2004;170:167.CrossRef
18.
Zurück zum Zitat Seftor E, Meltzer P, Schatteman G, et al. Expression of multiple molecular phenotypes by aggressive melanoma tumor cells: role in vasculogenic mimicry. Crit Rev Oncol Hematol. 2002;44:17–27.CrossRef Seftor E, Meltzer P, Schatteman G, et al. Expression of multiple molecular phenotypes by aggressive melanoma tumor cells: role in vasculogenic mimicry. Crit Rev Oncol Hematol. 2002;44:17–27.CrossRef
19.
Zurück zum Zitat Alberts S, Cervantes A, Van de Velde C. Gastric cancer: epidemiology, pathology and treatment. Ann Oncol. 2003;14:31–6. Alberts S, Cervantes A, Van de Velde C. Gastric cancer: epidemiology, pathology and treatment. Ann Oncol. 2003;14:31–6.
21.
Zurück zum Zitat Parkin D, Bray F, Ferlay J, et al. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74.CrossRefPubMed Parkin D, Bray F, Ferlay J, et al. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74.CrossRefPubMed
22.
Zurück zum Zitat Leroy X, Zini L, Franquet H, Kervoaze G, Villers A, Delehedde M, Copin MC, Lassalle P. Vascular endocan (ESM-1) is markedly overexpressed in clear cell renal cell carcinoma). Histopathology. 2009;56:180–7.CrossRef Leroy X, Zini L, Franquet H, Kervoaze G, Villers A, Delehedde M, Copin MC, Lassalle P. Vascular endocan (ESM-1) is markedly overexpressed in clear cell renal cell carcinoma). Histopathology. 2009;56:180–7.CrossRef
23.
Zurück zum Zitat Perey L, Benhattar J, Peters R, et al. High tumour contamination of leukaphereses in patients with small cell carcinoma of the lung: a comparison of immunocytochemistry and RT-PCR. Br J Cancer. 2001;85:1713.CrossRefPubMed Perey L, Benhattar J, Peters R, et al. High tumour contamination of leukaphereses in patients with small cell carcinoma of the lung: a comparison of immunocytochemistry and RT-PCR. Br J Cancer. 2001;85:1713.CrossRefPubMed
24.
Zurück zum Zitat Amatschek S, Koenig U, Auer H, et al. Tissue-wide expression profiling using cDNA subtraction and microarrays to identify tumor-specific genes.Cancer Res. 2004;64:844.CrossRefPubMed Amatschek S, Koenig U, Auer H, et al. Tissue-wide expression profiling using cDNA subtraction and microarrays to identify tumor-specific genes.Cancer Res. 2004;64:844.CrossRefPubMed
25.
Zurück zum Zitat Song Z, Gong P, Wu Y. Relationship between the expression of iNOS, VEGF, tumor angiogenesis and gastric cancer. World J Gastroenterol. 2002;8:591–5.PubMed Song Z, Gong P, Wu Y. Relationship between the expression of iNOS, VEGF, tumor angiogenesis and gastric cancer. World J Gastroenterol. 2002;8:591–5.PubMed
26.
Zurück zum Zitat Tanigawa N, Amaya H, Matsumura M, et al. Extent of tumor vascularization correlates with prognosis and hematogenous metastasis in gastric carcinomas. Cancer Res. 1996;56:2671.PubMed Tanigawa N, Amaya H, Matsumura M, et al. Extent of tumor vascularization correlates with prognosis and hematogenous metastasis in gastric carcinomas. Cancer Res. 1996;56:2671.PubMed
27.
Zurück zum Zitat Tenderenda M, Rutkowski P, Jesionek-Kupnicka D, et al. Expression of CD34 in gastric cancer and its correlation with histology, stage, proliferation activity, p53 expression and apoptotic index. Pathol Oncol Res. 2001;7:129–34.CrossRefPubMed Tenderenda M, Rutkowski P, Jesionek-Kupnicka D, et al. Expression of CD34 in gastric cancer and its correlation with histology, stage, proliferation activity, p53 expression and apoptotic index. Pathol Oncol Res. 2001;7:129–34.CrossRefPubMed
28.
Zurück zum Zitat Hanahan D, Folkman J, O’Reilly M, et al. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Curr Biol. 1995;5:10–3.CrossRef Hanahan D, Folkman J, O’Reilly M, et al. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Curr Biol. 1995;5:10–3.CrossRef
29.
Zurück zum Zitat McDonald D, Foss A. Endothelial cells of tumor vessels: abnormal but not absent. Cancer Metastasis Rev. 2000;19:109–20.CrossRef McDonald D, Foss A. Endothelial cells of tumor vessels: abnormal but not absent. Cancer Metastasis Rev. 2000;19:109–20.CrossRef
30.
Zurück zum Zitat Liekens S, De Clercq E, Neyts J. Angiogenesis: regulators and clinical applications. Biochem Pharmacol. 2001;61:253–70.CrossRefPubMed Liekens S, De Clercq E, Neyts J. Angiogenesis: regulators and clinical applications. Biochem Pharmacol. 2001;61:253–70.CrossRefPubMed
31.
Zurück zum Zitat Yasui W, Oue N, Aung P, et al. Molecular-pathological prognostic factors of gastric cancer: a review. Gastric Cancer. 2005;8:86–94.CrossRefPubMed Yasui W, Oue N, Aung P, et al. Molecular-pathological prognostic factors of gastric cancer: a review. Gastric Cancer. 2005;8:86–94.CrossRefPubMed
Metadaten
Titel
Overexpression of Endothelial Cell Specific Molecule-1 (ESM-1) in Gastric Cancer
verfasst von
Ni Liu, MD
Lian-hai Zhang, PhD
Hong Du, BS
Ying Hu, BS
Gui-guo Zhang, BS
Xiao-hong Wang, MD
Ji-you Li, PhD
Jia-fu Ji, MD
Publikationsdatum
01.10.2010
Verlag
Springer-Verlag
Erschienen in
Annals of Surgical Oncology / Ausgabe 10/2010
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-010-1037-9

Weitere Artikel der Ausgabe 10/2010

Annals of Surgical Oncology 10/2010 Zur Ausgabe

Update Chirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

S3-Leitlinie „Diagnostik und Therapie des Karpaltunnelsyndroms“

Karpaltunnelsyndrom BDC Leitlinien Webinare
CME: 2 Punkte

Das Karpaltunnelsyndrom ist die häufigste Kompressionsneuropathie peripherer Nerven. Obwohl die Anamnese mit dem nächtlichen Einschlafen der Hand (Brachialgia parästhetica nocturna) sehr typisch ist, ist eine klinisch-neurologische Untersuchung und Elektroneurografie in manchen Fällen auch eine Neurosonografie erforderlich. Im Anfangsstadium sind konservative Maßnahmen (Handgelenksschiene, Ergotherapie) empfehlenswert. Bei nicht Ansprechen der konservativen Therapie oder Auftreten von neurologischen Ausfällen ist eine Dekompression des N. medianus am Karpaltunnel indiziert.

Prof. Dr. med. Gregor Antoniadis
Berufsverband der Deutschen Chirurgie e.V.

S2e-Leitlinie „Distale Radiusfraktur“

Radiusfraktur BDC Leitlinien Webinare
CME: 2 Punkte

Das Webinar beschäftigt sich mit Fragen und Antworten zu Diagnostik und Klassifikation sowie Möglichkeiten des Ausschlusses von Zusatzverletzungen. Die Referenten erläutern, welche Frakturen konservativ behandelt werden können und wie. Das Webinar beantwortet die Frage nach aktuellen operativen Therapiekonzepten: Welcher Zugang, welches Osteosynthesematerial? Auf was muss bei der Nachbehandlung der distalen Radiusfraktur geachtet werden?

PD Dr. med. Oliver Pieske
Dr. med. Benjamin Meyknecht
Berufsverband der Deutschen Chirurgie e.V.

S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“

Appendizitis BDC Leitlinien Webinare
CME: 2 Punkte

Inhalte des Webinars zur S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“ sind die Darstellung des Projektes und des Erstellungswegs zur S1-Leitlinie, die Erläuterung der klinischen Relevanz der Klassifikation EAES 2015, die wissenschaftliche Begründung der wichtigsten Empfehlungen und die Darstellung stadiengerechter Therapieoptionen.

Dr. med. Mihailo Andric
Berufsverband der Deutschen Chirurgie e.V.