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- Publisher Website: 10.1038/onc.2010.170
- Scopus: eid_2-s2.0-77954959021
- PMID: 20498638
- WOS: WOS:000280151500005
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Article: Evidence for mesenchymal-like sub-populations within squamous cell carcinomas possessing chemoresistance and phenotypic plasticity
Title | Evidence for mesenchymal-like sub-populations within squamous cell carcinomas possessing chemoresistance and phenotypic plasticity |
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Authors | |
Keywords | chemotherapy resistance epithelial to mesenchymal transition head and neck squamous cell carcinoma tumor heterogeneity |
Issue Date | 2010 |
Citation | Oncogene, 2010, v. 29, n. 29, p. 4170-4182 How to Cite? |
Abstract | Variable drug responses among malignant cells within individual tumors may represent a barrier to their eradication using chemotherapy. Carcinoma cells expressing mesenchymal markers resist conventional and epidermal growth factor receptor (EGFR)-targeted chemotherapy. In this study, we evaluated whether mesenchymal-like sub-populations within human squamous cell carcinomas (SCCs) with predominantly epithelial features contribute to overall therapy resistance. We identified a mesenchymal-like subset expressing low E-cadherin (Ecad-lo) and high vimentin within the upper aerodigestive tract SCCs. This subset was both isolated from the cell lines and was identified in xenografts and primary clinical specimens. The Ecad-lo subset contained more low-turnover cells, correlating with resistance to the conventional chemotherapeutic paclitaxel in vitro. Epidermal growth factor induced less stimulation of the mitogen-activated protein kinase and phosphatidylinositol-3-kinase pathways in Ecad-lo cells, which was likely due to lower EGFR expression in this subset and correlated with in vivo resistance to the EGFR-targeted antibody, cetuximab. The Ecad-lo and high E-cadherin subsets were dynamic in phenotype, showing the capacity to repopulate each other from single-cell clones. Taken together, these results provide evidence for a low-turnover, mesenchymal-like sub-population in SCCs with diminished EGFR pathway function and intrinsic resistance to conventional and EGFR-targeted chemotherapies. © 2010 Macmillan Publishers Limited All rights reserved. |
Persistent Identifier | http://hdl.handle.net/10722/318479 |
ISSN | 2021 Impact Factor: 8.756 2020 SCImago Journal Rankings: 3.395 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Basu, D. | - |
dc.contributor.author | Nguyen, T. T.K. | - |
dc.contributor.author | Montone, K. T. | - |
dc.contributor.author | Zhang, G. | - |
dc.contributor.author | Wang, L. P. | - |
dc.contributor.author | Diehl, J. A. | - |
dc.contributor.author | Rustgi, A. K. | - |
dc.contributor.author | Lee, J. T. | - |
dc.contributor.author | Weinstein, G. S. | - |
dc.contributor.author | Herlyn, M. | - |
dc.date.accessioned | 2022-10-11T12:23:51Z | - |
dc.date.available | 2022-10-11T12:23:51Z | - |
dc.date.issued | 2010 | - |
dc.identifier.citation | Oncogene, 2010, v. 29, n. 29, p. 4170-4182 | - |
dc.identifier.issn | 0950-9232 | - |
dc.identifier.uri | http://hdl.handle.net/10722/318479 | - |
dc.description.abstract | Variable drug responses among malignant cells within individual tumors may represent a barrier to their eradication using chemotherapy. Carcinoma cells expressing mesenchymal markers resist conventional and epidermal growth factor receptor (EGFR)-targeted chemotherapy. In this study, we evaluated whether mesenchymal-like sub-populations within human squamous cell carcinomas (SCCs) with predominantly epithelial features contribute to overall therapy resistance. We identified a mesenchymal-like subset expressing low E-cadherin (Ecad-lo) and high vimentin within the upper aerodigestive tract SCCs. This subset was both isolated from the cell lines and was identified in xenografts and primary clinical specimens. The Ecad-lo subset contained more low-turnover cells, correlating with resistance to the conventional chemotherapeutic paclitaxel in vitro. Epidermal growth factor induced less stimulation of the mitogen-activated protein kinase and phosphatidylinositol-3-kinase pathways in Ecad-lo cells, which was likely due to lower EGFR expression in this subset and correlated with in vivo resistance to the EGFR-targeted antibody, cetuximab. The Ecad-lo and high E-cadherin subsets were dynamic in phenotype, showing the capacity to repopulate each other from single-cell clones. Taken together, these results provide evidence for a low-turnover, mesenchymal-like sub-population in SCCs with diminished EGFR pathway function and intrinsic resistance to conventional and EGFR-targeted chemotherapies. © 2010 Macmillan Publishers Limited All rights reserved. | - |
dc.language | eng | - |
dc.relation.ispartof | Oncogene | - |
dc.subject | chemotherapy resistance | - |
dc.subject | epithelial to mesenchymal transition | - |
dc.subject | head and neck | - |
dc.subject | squamous cell carcinoma | - |
dc.subject | tumor heterogeneity | - |
dc.title | Evidence for mesenchymal-like sub-populations within squamous cell carcinomas possessing chemoresistance and phenotypic plasticity | - |
dc.type | Article | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1038/onc.2010.170 | - |
dc.identifier.pmid | 20498638 | - |
dc.identifier.scopus | eid_2-s2.0-77954959021 | - |
dc.identifier.volume | 29 | - |
dc.identifier.issue | 29 | - |
dc.identifier.spage | 4170 | - |
dc.identifier.epage | 4182 | - |
dc.identifier.eissn | 1476-5594 | - |
dc.identifier.isi | WOS:000280151500005 | - |