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Article: The Enhanced metastatic potential of hepatocellular carcinoma (HCC) cells with sorafenib resistance

TitleThe Enhanced metastatic potential of hepatocellular carcinoma (HCC) cells with sorafenib resistance
Authors
Issue Date2013
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
PLoS One, 2013, v. 8 n. 11, p. e78675 How to Cite?
AbstractAcquired resistance towards sorafenib treatment was found in HCC patients, which results in poor prognosis. To investigate the enhanced metastatic potential of sorafenib resistance cells, sorafenib-resistant (SorR) cell lines were established by long-term exposure of the HCC cells to the maximum tolerated dose of sorafenib. Cell proliferation assay and qPCR of ABC transporter genes (ABCC1-3) were first performed to confirm the resistance of cells. Migration and invasion assays, and immunoblotting analysis on the expression of epithelial to mesenchymal transition (EMT) regulatory proteins were performed to study the metastatic potential of SorR cells. The expression of CD44 and CD133 were studied by flow cytometry and the gene expressions of pluripotency factors were studied by qPCR to demonstrate the enrichment of cancer stem cells (CSCs) in SorR cells. Control (CTL) and SorR cells were also injected orthotopically to the livers of NOD-SCID mice to investigate the development of lung metastasis. Increased expressions of ABCC1-3 were found in SorR cells. Enhanced migratory and invasive abilities of SorR cells were observed. The changes in expression of EMT regulatory proteins demonstrated an activation of the EMT process in SorR cells. Enriched proportion of CD44+ and CD44+CD133 + cells were also observed in SorR cells. All (8/8) mice injected with SorR cells demonstrated lung metastasis whereas only 1/8 mouse injected with CTL cells showed lung metastasis. HCC cells with sorafenib resistance demonstrated a higher metastatic potential, which may be due to the activated EMT process. Enriched CSCs were also demonstrated in the sorafenib resistant cells. This study suggests that advanced HCC patients with acquired sorafenib resistance may have enhanced tumor growth or distant metastasis, which raises the concern of long-term sorafenib treatment in advanced HCC patients who have developed resistance of sorafenib. © 2013 Chow et al.
Persistent Identifierhttp://hdl.handle.net/10722/193237
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChow, Ariel Ka Manen_US
dc.contributor.authorNg, Luien_US
dc.contributor.authorLam, Colin Siu Chien_US
dc.contributor.authorWong, Sunny Kit Manen_US
dc.contributor.authorWan, Timothy Ming Hunen_US
dc.contributor.authorCheng, Nathan Shiu Manen_US
dc.contributor.authorYau, Thomas Chung Cheungen_US
dc.contributor.authorPoon, Ronnie Tung Pingen_US
dc.contributor.authorPang, Roberta Wen Chien_US
dc.date.accessioned2013-12-20T02:37:55Z-
dc.date.available2013-12-20T02:37:55Z-
dc.date.issued2013en_US
dc.identifier.citationPLoS One, 2013, v. 8 n. 11, p. e78675en_US
dc.identifier.issn1932-6203-
dc.identifier.urihttp://hdl.handle.net/10722/193237-
dc.description.abstractAcquired resistance towards sorafenib treatment was found in HCC patients, which results in poor prognosis. To investigate the enhanced metastatic potential of sorafenib resistance cells, sorafenib-resistant (SorR) cell lines were established by long-term exposure of the HCC cells to the maximum tolerated dose of sorafenib. Cell proliferation assay and qPCR of ABC transporter genes (ABCC1-3) were first performed to confirm the resistance of cells. Migration and invasion assays, and immunoblotting analysis on the expression of epithelial to mesenchymal transition (EMT) regulatory proteins were performed to study the metastatic potential of SorR cells. The expression of CD44 and CD133 were studied by flow cytometry and the gene expressions of pluripotency factors were studied by qPCR to demonstrate the enrichment of cancer stem cells (CSCs) in SorR cells. Control (CTL) and SorR cells were also injected orthotopically to the livers of NOD-SCID mice to investigate the development of lung metastasis. Increased expressions of ABCC1-3 were found in SorR cells. Enhanced migratory and invasive abilities of SorR cells were observed. The changes in expression of EMT regulatory proteins demonstrated an activation of the EMT process in SorR cells. Enriched proportion of CD44+ and CD44+CD133 + cells were also observed in SorR cells. All (8/8) mice injected with SorR cells demonstrated lung metastasis whereas only 1/8 mouse injected with CTL cells showed lung metastasis. HCC cells with sorafenib resistance demonstrated a higher metastatic potential, which may be due to the activated EMT process. Enriched CSCs were also demonstrated in the sorafenib resistant cells. This study suggests that advanced HCC patients with acquired sorafenib resistance may have enhanced tumor growth or distant metastasis, which raises the concern of long-term sorafenib treatment in advanced HCC patients who have developed resistance of sorafenib. © 2013 Chow et al.-
dc.languageengen_US
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action-
dc.relation.ispartofPLoS Oneen_US
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleThe Enhanced metastatic potential of hepatocellular carcinoma (HCC) cells with sorafenib resistanceen_US
dc.typeArticleen_US
dc.identifier.emailChow, KM: chowakm@hku.hken_US
dc.identifier.emailNg, L: luing@hku.hken_US
dc.identifier.emailLam, SC: colin88@hku.hken_US
dc.identifier.emailWan, TMH: tmhwan@hku.hken_US
dc.identifier.emailCheng, SM: nathanc@hku.hken_US
dc.identifier.emailYau, TCC: tyaucc@hku.hken_US
dc.identifier.emailPoon, RTP: poontp@hku.hken_US
dc.identifier.emailPang, RWC: robertap@hku.hken_US
dc.identifier.authorityYau, TCC=rp01466en_US
dc.identifier.authorityPoon, RTP=rp00446en_US
dc.identifier.authorityPang, RWC=rp00274en_US
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0078675-
dc.identifier.pmid24244338-
dc.identifier.pmcidPMC3823841-
dc.identifier.scopuseid_2-s2.0-84892920174-
dc.identifier.hkuros227159en_US
dc.identifier.volume8en_US
dc.identifier.issue11en_US
dc.identifier.spagee78675en_US
dc.identifier.epagee78675en_US
dc.identifier.isiWOS:000327221600047-
dc.publisher.placeUnited States-

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