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Article: Reduced expression of EphB2 that parallels invasion and metastasis in colorectal tumours

TitleReduced expression of EphB2 that parallels invasion and metastasis in colorectal tumours
Authors
Issue Date2006
PublisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/
Citation
Carcinogenesis, 2006, v. 27 n. 3, p. 454-464 How to Cite?
Abstract
EphB2, a receptor tyrosine kinase regulated by the β-catenin/Tcf4 complex, is expressed in the proliferative compartment of mouse intestine and regulates bidirectional migration of intestinal precursor cells in the crypt-villus axis through repulsive interaction with Ephrin-B ligands. Recently, it has been shown that reduction of EphB activity accelerates colon tumour progression in the ApcMin/+ mice. In this study, we examined the expression of EphB2 in normal colon, adenomas, primary colorectal cancers (CRCs), lymph node metastases and liver metastases using immunohistochemistry on tissue microarrays. In addition, EphB2 was overexpressed in SW480 colon cancer cells to study its effect in vitro. We found that EphB2 was expressed in 100% of normal colon crypt base cells, 78% of adenomas, 55.4% of primary CRCs, 37.8% of lymph node metastases and 32.9% of liver metastases (all differences were statistically significant at P < 0.001 compared with primary CRCs). Patients with CRCs that lose EphB2 expression had more advanced tumour stage (P=0.005), poor differentiation (P=<0.001), poor overall survival (P=0.005) and disease-free survival (P=0.001), with the latter being independent of tumour stage. In vitro studies showed that overexpression of EphB2 inhibited colon cancer cell growth in colony formation assay and activation of EphB2 receptor inhibited colon cancer cell adhesion and migration. Our data demonstrated a progressive loss of EphB2 expression in each critical step of colon carcinogenesis, including the onset of invasion, dedifferentiation and metastasis which are paralleled by adverse patient outcome. EphB2 may achieve its tumour suppressor function through regulation of cell survival, adhesion and migration. © 2006 Oxford University Press.
Persistent Identifierhttp://hdl.handle.net/10722/148454
ISSN
2013 Impact Factor: 5.266
ISI Accession Number ID
References

 

Author Affiliations
  1. University of California, San Francisco
  2. The University of Hong Kong
  3. Peking University
DC FieldValueLanguage
dc.contributor.authorGuo, DLen_US
dc.contributor.authorZhang, Jen_US
dc.contributor.authorYuen, STen_US
dc.contributor.authorTsui, WYen_US
dc.contributor.authorChan, ASYen_US
dc.contributor.authorHo, Cen_US
dc.contributor.authorJi, Jen_US
dc.contributor.authorLeung, SYen_US
dc.contributor.authorChen, Xen_US
dc.date.accessioned2012-05-29T06:13:04Z-
dc.date.available2012-05-29T06:13:04Z-
dc.date.issued2006en_US
dc.identifier.citationCarcinogenesis, 2006, v. 27 n. 3, p. 454-464en_US
dc.identifier.issn0143-3334en_US
dc.identifier.urihttp://hdl.handle.net/10722/148454-
dc.description.abstractEphB2, a receptor tyrosine kinase regulated by the β-catenin/Tcf4 complex, is expressed in the proliferative compartment of mouse intestine and regulates bidirectional migration of intestinal precursor cells in the crypt-villus axis through repulsive interaction with Ephrin-B ligands. Recently, it has been shown that reduction of EphB activity accelerates colon tumour progression in the ApcMin/+ mice. In this study, we examined the expression of EphB2 in normal colon, adenomas, primary colorectal cancers (CRCs), lymph node metastases and liver metastases using immunohistochemistry on tissue microarrays. In addition, EphB2 was overexpressed in SW480 colon cancer cells to study its effect in vitro. We found that EphB2 was expressed in 100% of normal colon crypt base cells, 78% of adenomas, 55.4% of primary CRCs, 37.8% of lymph node metastases and 32.9% of liver metastases (all differences were statistically significant at P < 0.001 compared with primary CRCs). Patients with CRCs that lose EphB2 expression had more advanced tumour stage (P=0.005), poor differentiation (P=<0.001), poor overall survival (P=0.005) and disease-free survival (P=0.001), with the latter being independent of tumour stage. In vitro studies showed that overexpression of EphB2 inhibited colon cancer cell growth in colony formation assay and activation of EphB2 receptor inhibited colon cancer cell adhesion and migration. Our data demonstrated a progressive loss of EphB2 expression in each critical step of colon carcinogenesis, including the onset of invasion, dedifferentiation and metastasis which are paralleled by adverse patient outcome. EphB2 may achieve its tumour suppressor function through regulation of cell survival, adhesion and migration. © 2006 Oxford University Press.en_US
dc.languageengen_US
dc.publisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/en_US
dc.relation.ispartofCarcinogenesisen_US
dc.rightsCarcinogenesis. Copyright © Oxford University Press.-
dc.subject.meshAdenoma - Genetics - Pathologyen_US
dc.subject.meshAdulten_US
dc.subject.meshAgeden_US
dc.subject.meshAged, 80 And Overen_US
dc.subject.meshCell Survivalen_US
dc.subject.meshCell Transformation, Neoplasticen_US
dc.subject.meshColon - Enzymologyen_US
dc.subject.meshColorectal Neoplasms - Genetics - Pathologyen_US
dc.subject.meshDisease-Free Survivalen_US
dc.subject.meshDown-Regulationen_US
dc.subject.meshFemaleen_US
dc.subject.meshGene Expression Profilingen_US
dc.subject.meshHumansen_US
dc.subject.meshLiver Neoplasms - Secondaryen_US
dc.subject.meshLymphatic Metastasisen_US
dc.subject.meshMaleen_US
dc.subject.meshMiddle Ageden_US
dc.subject.meshNeoplasm Invasivenessen_US
dc.subject.meshNeoplasm Metastasisen_US
dc.subject.meshNeoplasm Stagingen_US
dc.subject.meshPrognosisen_US
dc.subject.meshReceptor, Ephb2 - Biosynthesisen_US
dc.titleReduced expression of EphB2 that parallels invasion and metastasis in colorectal tumoursen_US
dc.typeArticleen_US
dc.identifier.emailLeung, SY:suetyi@hkucc.hku.hken_US
dc.identifier.authorityLeung, SY=rp00359en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1093/carcin/bgi259en_US
dc.identifier.pmid16272170en_US
dc.identifier.scopuseid_2-s2.0-33644866330en_US
dc.identifier.hkuros113971-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33644866330&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume27en_US
dc.identifier.issue3en_US
dc.identifier.spage454en_US
dc.identifier.epage464en_US
dc.identifier.isiWOS:000235771300011-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.citeulike526215-

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