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dc.contributor.authorStovold, Rachel
dc.contributor.authorMeredith, S
dc.contributor.authorBryant, J
dc.contributor.authorBabur, M
dc.contributor.authorWilliams, K
dc.contributor.authorDean, Emma J
dc.contributor.authorDive, Caroline
dc.contributor.authorBlackhall, Fiona H
dc.contributor.authorWhite, A
dc.date.accessioned2013-05-20T13:05:45Z
dc.date.available2013-05-20T13:05:45Z
dc.date.issued2013-03-21
dc.identifier.citationNeuroendocrine and epithelial phenotypes in small-cell lung cancer: implications for metastasis and survival in patients. 2013: Br J Canceren_GB
dc.identifier.issn1532-1827
dc.identifier.pmid23519056
dc.identifier.doi10.1038/bjc.2013.112
dc.identifier.urihttp://hdl.handle.net/10541/292383
dc.description.abstractBackground:Small-cell lung cancer (SCLC) has a very aggressive clinical course with early metastasis. This study investigated how the distinctive neuroendocrine characteristics contribute to disease progression and invasion in human SCLC.Methods:The neuroendocrine phenotype (pro-opiomelanocortin (POMC)) was quantified by ELISA in blood samples from 43 SCLC patients. The neuroendocrine (POMC, chromogranin A, neuron-specific enolase, NCAM) and epithelial (cytokeratin and E-cadherin) phenotypes were investigated, using ELISA and immunocytochemistry/immunohistochemistry.Results:In SCLC patients, 16% had elevated circulating POMC, which was associated with significantly worse survival (P=0.02) and liver metastases (P=0.004). In addition, POMC correlated with epithelial-positive circulating tumour cells (P=0.0002). In a panel of SCLC cell lines, all POMC-secreting cell lines expressed cytokeratin (40% of total). Even after cloning, DMS 79 cells expressed both neuroendocrine and epithelial markers. DMS 79 xenografts secreted POMC into the blood, which mirrored the tumour volume. These xenografts expressed both neuroendocrine and epithelial phenotypes in all tumours, with both phenotypes prevalent in cells invading the surrounding tissue.Conclusion:Both neuroendocrine and epithelial phenotypes coexist in human SCLC tumours in vitro and in vivo and this persists in invading tumour cells. In patients, POMC secretion predicts poor survival and liver metastases, suggesting a crucial role of the neuroendocrine phenotype.British Journal of Cancer advance online publication, 21 March 2013; doi:10.1038/bjc.2013.112 www.bjcancer.com.
dc.languageENG
dc.language.isoenen
dc.rightsArchived with thanks to British journal of canceren_GB
dc.titleNeuroendocrine and epithelial phenotypes in small-cell lung cancer: implications for metastasis and survival in patients.en
dc.typeArticleen
dc.contributor.department1] Faculty of Life Sciences, Manchester Academic Health Sciences Centre, University of Manchester, 3.016 AV Hill Building, Manchester M13 9PT, UK [2] Paterson Institute for Cancer Research, University of Manchester, Manchester M20 4BX, UK.en_GB
dc.identifier.journalBritish Journal of Canceren_GB
html.description.abstractBackground:Small-cell lung cancer (SCLC) has a very aggressive clinical course with early metastasis. This study investigated how the distinctive neuroendocrine characteristics contribute to disease progression and invasion in human SCLC.Methods:The neuroendocrine phenotype (pro-opiomelanocortin (POMC)) was quantified by ELISA in blood samples from 43 SCLC patients. The neuroendocrine (POMC, chromogranin A, neuron-specific enolase, NCAM) and epithelial (cytokeratin and E-cadherin) phenotypes were investigated, using ELISA and immunocytochemistry/immunohistochemistry.Results:In SCLC patients, 16% had elevated circulating POMC, which was associated with significantly worse survival (P=0.02) and liver metastases (P=0.004). In addition, POMC correlated with epithelial-positive circulating tumour cells (P=0.0002). In a panel of SCLC cell lines, all POMC-secreting cell lines expressed cytokeratin (40% of total). Even after cloning, DMS 79 cells expressed both neuroendocrine and epithelial markers. DMS 79 xenografts secreted POMC into the blood, which mirrored the tumour volume. These xenografts expressed both neuroendocrine and epithelial phenotypes in all tumours, with both phenotypes prevalent in cells invading the surrounding tissue.Conclusion:Both neuroendocrine and epithelial phenotypes coexist in human SCLC tumours in vitro and in vivo and this persists in invading tumour cells. In patients, POMC secretion predicts poor survival and liver metastases, suggesting a crucial role of the neuroendocrine phenotype.British Journal of Cancer advance online publication, 21 March 2013; doi:10.1038/bjc.2013.112 www.bjcancer.com.


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