File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Non-small cell lung cancer cells expressing CD44 are enriched for stem cell-like properties

TitleNon-small cell lung cancer cells expressing CD44 are enriched for stem cell-like properties
Authors
Issue Date2010
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
Plos One, 2010, v. 5 n. 11 How to Cite?
AbstractBackground: The cancer stem cell theory hypothesizes that cancers are perpetuated by cancer stem cells (CSC) or tumor initiating cells (TIC) possessing self-renewal and other stem cell-like properties while differentiated non-stem/initiating cells have a finite life span. To investigate whether the hypothesis is applicable to lung cancer, identification of lung CSC and demonstration of these capacities is essential. Methodology/Principal Finding: The expression profiles of five stem cell markers (CD34, CD44, CD133, BMI1 and OCT4) were screened by flow cytometry in 10 lung cancer cell lines. CD44 was further investigated by testing for in vitro and in vivo tumorigenecity. Formation of spheroid bodies and in vivo tumor initiation ability were demonstrated in CD44+ cells of 4 cell lines. Serial in vivo tumor transplantability in nude mice was demonstrated using H1299 cell line. The primary xenografts initiated from CD44+ cells consisted of mixed CD44+ and CD44- cells in similar ratio as the parental H1299 cell line, supporting in vivo differentiation. Semi-quantitative Real-Time PCR (RT-PCR) showed that both freshly sorted CD44+ and CD44+ cells derived from CD44+-initiated tumors expressed the pluripotency genes OCT4/POU5F1, NANOG, SOX2. These stemness markers were not expressed by CD44- cells. Furthermore, freshly sorted CD44+ cells were more resistant to cisplatin treatment with lower apoptosis levels than CD44- cells. Immunohistochemical analysis of 141 resected non-small cell lung cancers showed tumor cell expression of CD44 in 50.4% of tumors while no CD34, and CD133 expression was observed in tumor cells. CD44 expression was associated with squamous cell carcinoma but unexpectedly, a longer survival was observed in CD44-expressing adenocarcinomas. Conclusion/Significance: Overall, our results demonstrated that stem cell-like properties are enriched in CD44-expressing subpopulations of some lung cancer cell lines. Further investigation is required to clarify the role of CD44 in tumor cell renewal and cancer propagation in the in vivo environment.© 2010 Leung et al.
Persistent Identifierhttp://hdl.handle.net/10722/139937
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
HKU10400863
200907176141
China Medical Board, University of Hong Kong
National Institutes of HealthR01HL087948
National Cancer InstituteR21CA131522
DOE at Nevada Cancer InstituteDOE-FG02-08ER64608
Nevada Cancer Institute
University of Southern Nevada
Funding Information:

This work was supported by a Seed Fund for Basic Research (HKU 10400863 to M. P. Wong), a small project grant (HKU 200907176141 to E. L. Leung) and an overseas research training grant from China Medical Board, University of Hong Kong, awarded to E. L. Leung. This work was also supported in part by National Institutes of Health Grants R01HL087948, National Cancer Institute Grant R21CA131522 (to Y. Ma). DOE Funding DOE-FG02-08ER64608 at Nevada Cancer Institute (to L. M. Fink), a Startup Funding from the Nevada Cancer Institute and the University of Southern Nevada (to R. R. Fiscus). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References

 

DC FieldValueLanguage
dc.contributor.authorLeung, ELHen_HK
dc.contributor.authorFiscus, RRen_HK
dc.contributor.authorTung, JWen_HK
dc.contributor.authorTin, VPCen_HK
dc.contributor.authorCheng, LCen_HK
dc.contributor.authorSihoe, ADLen_HK
dc.contributor.authorFink, LMen_HK
dc.contributor.authorMa, Yen_HK
dc.contributor.authorWong, MPen_HK
dc.date.accessioned2011-09-23T06:02:02Z-
dc.date.available2011-09-23T06:02:02Z-
dc.date.issued2010en_HK
dc.identifier.citationPlos One, 2010, v. 5 n. 11en_HK
dc.identifier.issn1932-6203en_HK
dc.identifier.urihttp://hdl.handle.net/10722/139937-
dc.description.abstractBackground: The cancer stem cell theory hypothesizes that cancers are perpetuated by cancer stem cells (CSC) or tumor initiating cells (TIC) possessing self-renewal and other stem cell-like properties while differentiated non-stem/initiating cells have a finite life span. To investigate whether the hypothesis is applicable to lung cancer, identification of lung CSC and demonstration of these capacities is essential. Methodology/Principal Finding: The expression profiles of five stem cell markers (CD34, CD44, CD133, BMI1 and OCT4) were screened by flow cytometry in 10 lung cancer cell lines. CD44 was further investigated by testing for in vitro and in vivo tumorigenecity. Formation of spheroid bodies and in vivo tumor initiation ability were demonstrated in CD44+ cells of 4 cell lines. Serial in vivo tumor transplantability in nude mice was demonstrated using H1299 cell line. The primary xenografts initiated from CD44+ cells consisted of mixed CD44+ and CD44- cells in similar ratio as the parental H1299 cell line, supporting in vivo differentiation. Semi-quantitative Real-Time PCR (RT-PCR) showed that both freshly sorted CD44+ and CD44+ cells derived from CD44+-initiated tumors expressed the pluripotency genes OCT4/POU5F1, NANOG, SOX2. These stemness markers were not expressed by CD44- cells. Furthermore, freshly sorted CD44+ cells were more resistant to cisplatin treatment with lower apoptosis levels than CD44- cells. Immunohistochemical analysis of 141 resected non-small cell lung cancers showed tumor cell expression of CD44 in 50.4% of tumors while no CD34, and CD133 expression was observed in tumor cells. CD44 expression was associated with squamous cell carcinoma but unexpectedly, a longer survival was observed in CD44-expressing adenocarcinomas. Conclusion/Significance: Overall, our results demonstrated that stem cell-like properties are enriched in CD44-expressing subpopulations of some lung cancer cell lines. Further investigation is required to clarify the role of CD44 in tumor cell renewal and cancer propagation in the in vivo environment.© 2010 Leung et al.en_HK
dc.languageengen_US
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.actionen_HK
dc.relation.ispartofPLoS ONEen_HK
dc.subject.meshAntigens, CD44 - genetics - metabolism-
dc.subject.meshCarcinoma, Non-Small-Cell Lung - genetics - metabolism - pathology-
dc.subject.meshLung Neoplasms - genetics - metabolism - pathology-
dc.subject.meshNeoplastic Stem Cells - metabolism - pathology-
dc.subject.meshPeptides - genetics - metabolism-
dc.titleNon-small cell lung cancer cells expressing CD44 are enriched for stem cell-like propertiesen_HK
dc.typeArticleen_HK
dc.identifier.emailWong, MP:mwpik@hkucc.hku.hken_HK
dc.identifier.authorityWong, MP=rp00348en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0014062en_HK
dc.identifier.pmid21124918-
dc.identifier.pmcidPMC2988826-
dc.identifier.scopuseid_2-s2.0-78649522166en_HK
dc.identifier.hkuros192493en_US
dc.identifier.hkuros247040-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-78649522166&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume5en_HK
dc.identifier.issue11en_HK
dc.identifier.spagee14062en_US
dc.identifier.epagee14062en_US
dc.identifier.eissn1932-6203-
dc.identifier.isiWOS:000284400100011-
dc.publisher.placeUnited Statesen_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats