Neuroendocrine and epithelial phenotypes in small-cell lung cancer: implications for metastasis and survival in patients
Background: 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...
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Published in | British journal of cancer Vol. 108; no. 8; pp. 1704 - 1711 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
30.04.2013
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | Background:
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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work. |
ISSN: | 0007-0920 1532-1827 |
DOI: | 10.1038/bjc.2013.112 |