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Article: Decreased adhesiveness, resistance to anoikis and suppression of GRP94 are integral to the survival of circulating tumor cells in prostate cancer

TitleDecreased adhesiveness, resistance to anoikis and suppression of GRP94 are integral to the survival of circulating tumor cells in prostate cancer
Authors
KeywordsAdhesiveness
Anoikis
Circulating tumor cell
GRP94
Metastasis
Issue Date2008
PublisherSpringer Verlag Dordrecht. The Journal's web site is located at http://springerlink.metapress.com/openurl.asp?genre=journal&issn=0262-0898
Citation
Clinical And Experimental Metastasis, 2008, v. 25 n. 5, p. 497-508 How to Cite?
AbstractThe presence of circulating tumor cells (CTC) is common in prostate cancer patients, however until recently their clinical significance was unknown. The CTC stage is essential for the formation of distant metastases, and their continuing presence after radical prostatectomy has been shown to predict recurrent or latent disease. Despite their mechanistic and prognostic importance, due both to their scarcity and difficulties in their isolation, little is known about the characteristics that enable their production and survival. The aim of this study was to investigate the molecular mechanisms underlying the survival of CTC cells. A novel CTC cell line from the bloodstream of an orthotopic mouse model of castration-resistant prostate cancer was established and compared with the primary tumor using attachment assays, detachment culture, Western blot, flow cytometry and 2D gel electrophoresis. Decreased adhesiveness and expression of adhesion molecules E-cadherin, β4-integrin and γ-catenin, together with resistance to detachment and drug-induced apoptosis and upregulation of Bcl-2 were integral to the development of CTC and their survival. Using proteomic studies, we observed that the GRP94 glycoprotein was suppressed in CTC. GRP94 was also shown to be suppressed in a tissue microarray study of 79 prostate cancer patients, indicating its possible role in prostate cancer progression. Overall, this study suggests molecular alterations accounting for the release and survival of CTC, which may be used as drug targets for either anti-metastatic therapy or the suppression of latent disease. We also indicate the novel involvement of GRP94 suppression in prostate cancer metastasis. © 2008 Springer Science+Business Media B.V.
Persistent Identifierhttp://hdl.handle.net/10722/67441
ISSN
2015 Impact Factor: 2.728
2015 SCImago Journal Rankings: 1.338
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorHoward, EWen_HK
dc.contributor.authorLeung, SCLen_HK
dc.contributor.authorYuen, HFen_HK
dc.contributor.authorChua, CWen_HK
dc.contributor.authorLee, DTen_HK
dc.contributor.authorChan, KWen_HK
dc.contributor.authorWang, Xen_HK
dc.contributor.authorWong, YCen_HK
dc.date.accessioned2010-09-06T05:55:10Z-
dc.date.available2010-09-06T05:55:10Z-
dc.date.issued2008en_HK
dc.identifier.citationClinical And Experimental Metastasis, 2008, v. 25 n. 5, p. 497-508en_HK
dc.identifier.issn0262-0898en_HK
dc.identifier.urihttp://hdl.handle.net/10722/67441-
dc.description.abstractThe presence of circulating tumor cells (CTC) is common in prostate cancer patients, however until recently their clinical significance was unknown. The CTC stage is essential for the formation of distant metastases, and their continuing presence after radical prostatectomy has been shown to predict recurrent or latent disease. Despite their mechanistic and prognostic importance, due both to their scarcity and difficulties in their isolation, little is known about the characteristics that enable their production and survival. The aim of this study was to investigate the molecular mechanisms underlying the survival of CTC cells. A novel CTC cell line from the bloodstream of an orthotopic mouse model of castration-resistant prostate cancer was established and compared with the primary tumor using attachment assays, detachment culture, Western blot, flow cytometry and 2D gel electrophoresis. Decreased adhesiveness and expression of adhesion molecules E-cadherin, β4-integrin and γ-catenin, together with resistance to detachment and drug-induced apoptosis and upregulation of Bcl-2 were integral to the development of CTC and their survival. Using proteomic studies, we observed that the GRP94 glycoprotein was suppressed in CTC. GRP94 was also shown to be suppressed in a tissue microarray study of 79 prostate cancer patients, indicating its possible role in prostate cancer progression. Overall, this study suggests molecular alterations accounting for the release and survival of CTC, which may be used as drug targets for either anti-metastatic therapy or the suppression of latent disease. We also indicate the novel involvement of GRP94 suppression in prostate cancer metastasis. © 2008 Springer Science+Business Media B.V.en_HK
dc.languageengen_HK
dc.publisherSpringer Verlag Dordrecht. The Journal's web site is located at http://springerlink.metapress.com/openurl.asp?genre=journal&issn=0262-0898en_HK
dc.relation.ispartofClinical and Experimental Metastasisen_HK
dc.subjectAdhesivenessen_HK
dc.subjectAnoikisen_HK
dc.subjectCirculating tumor cellen_HK
dc.subjectGRP94en_HK
dc.subjectMetastasisen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshAnoikis - physiologyen_HK
dc.subject.meshBlotting, Westernen_HK
dc.subject.meshCell Adhesion - physiologyen_HK
dc.subject.meshCell Line, Tumoren_HK
dc.subject.meshCell Survival - physiologyen_HK
dc.subject.meshFlow Cytometryen_HK
dc.subject.meshHSP70 Heat-Shock Proteins - metabolismen_HK
dc.subject.meshHumansen_HK
dc.subject.meshImmunohistochemistryen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMembrane Proteins - metabolismen_HK
dc.subject.meshMiceen_HK
dc.subject.meshNeoplastic Cells, Circulating - metabolismen_HK
dc.subject.meshProstatic Neoplasms - blood - pathologyen_HK
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_HK
dc.subject.meshTissue Array Analysisen_HK
dc.titleDecreased adhesiveness, resistance to anoikis and suppression of GRP94 are integral to the survival of circulating tumor cells in prostate canceren_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0262-0898&volume=25&spage=497&epage=508&date=2008&atitle=Decreased+adhesiveness,+resistance+to+anoikis+and+suppression+of+GRP94+are+integral+to+the+survival+of+circulating+tumor+cells+in+prostate+canceren_HK
dc.identifier.emailChan, KW:hrmtckw@hku.hken_HK
dc.identifier.emailWong, YC:ycwong@hkucc.hku.hken_HK
dc.identifier.authorityChan, KW=rp00330en_HK
dc.identifier.authorityWong, YC=rp00316en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1007/s10585-008-9157-3en_HK
dc.identifier.pmid18340425-
dc.identifier.scopuseid_2-s2.0-48349095124en_HK
dc.identifier.hkuros147348en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-48349095124&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume25en_HK
dc.identifier.issue5en_HK
dc.identifier.spage497en_HK
dc.identifier.epage508en_HK
dc.identifier.isiWOS:000257719400001-
dc.publisher.placeNetherlandsen_HK
dc.identifier.scopusauthoridHoward, EW=16480736900en_HK
dc.identifier.scopusauthoridLeung, SCL=36894169100en_HK
dc.identifier.scopusauthoridYuen, HF=14018633400en_HK
dc.identifier.scopusauthoridChua, CW=9437494600en_HK
dc.identifier.scopusauthoridLee, DT=7406666118en_HK
dc.identifier.scopusauthoridChan, KW=16444133100en_HK
dc.identifier.scopusauthoridWang, X=7501854829en_HK
dc.identifier.scopusauthoridWong, YC=7403041798en_HK

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