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

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TitleReduced expression of EphB2 that parallels invasion and metastasis in colorectal tumours
AuthorsGuo, DL2
Zhang, J1 3
Yuen, ST2
Tsui, WY2
Chan, ASY2
Ho, C1
Ji, J3
Leung, SY2
Chen, X1
Issue Date2006
PublisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/
CitationCarcinogenesis, 2006, v. 27 n. 3, p. 454-464 [How to Cite?]
DOI: http://dx.doi.org/10.1093/carcin/bgi259
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.
ISSN0143-3334
2011 Impact Factor: 5.702
2011 SCImago Journal Rankings: 0.692
DOIhttp://dx.doi.org/10.1093/carcin/bgi259
ISI Accession Number IDWOS:000235771300011
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorGuo, DL
dc.contributor.authorZhang, J
dc.contributor.authorYuen, ST
dc.contributor.authorTsui, WY
dc.contributor.authorChan, ASY
dc.contributor.authorHo, C
dc.contributor.authorJi, J
dc.contributor.authorLeung, SY
dc.contributor.authorChen, X
dc.date.accessioned2012-05-29T06:13:04Z
dc.date.available2012-05-29T06:13:04Z
dc.date.issued2006
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.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationCarcinogenesis, 2006, v. 27 n. 3, p. 454-464 [How to Cite?]
DOI: http://dx.doi.org/10.1093/carcin/bgi259
dc.identifier.citeulike526215
dc.identifier.doihttp://dx.doi.org/10.1093/carcin/bgi259
dc.identifier.epage464
dc.identifier.hkuros113971
dc.identifier.isiWOS:000235771300011
dc.identifier.issn0143-3334
2011 Impact Factor: 5.702
2011 SCImago Journal Rankings: 0.692
dc.identifier.issue3
dc.identifier.pmid16272170
dc.identifier.scopuseid_2-s2.0-33644866330
dc.identifier.spage454
dc.identifier.urihttp://hdl.handle.net/10722/148454
dc.identifier.volume27
dc.languageeng
dc.publisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/
dc.publisher.placeUnited Kingdom
dc.relation.ispartofCarcinogenesis
dc.relation.referencesReferences in Scopus
dc.rightsCarcinogenesis. Copyright © Oxford University Press.
dc.subject.meshAdenoma - Genetics - Pathology
dc.subject.meshAdult
dc.subject.meshAged
dc.subject.meshAged, 80 And Over
dc.subject.meshCell Survival
dc.subject.meshCell Transformation, Neoplastic
dc.subject.meshColon - Enzymology
dc.subject.meshColorectal Neoplasms - Genetics - Pathology
dc.subject.meshDisease-Free Survival
dc.subject.meshDown-Regulation
dc.subject.meshFemale
dc.subject.meshGene Expression Profiling
dc.subject.meshHumans
dc.subject.meshLiver Neoplasms - Secondary
dc.subject.meshLymphatic Metastasis
dc.subject.meshMale
dc.subject.meshMiddle Aged
dc.subject.meshNeoplasm Invasiveness
dc.subject.meshNeoplasm Metastasis
dc.subject.meshNeoplasm Staging
dc.subject.meshPrognosis
dc.subject.meshReceptor, Ephb2 - Biosynthesis
dc.titleReduced expression of EphB2 that parallels invasion and metastasis in colorectal tumours
dc.typeArticle
Author Affiliations
  1. University of California, San Francisco
  2. The University of Hong Kong
  3. Peking University