CD133+ cancer stem-like cells in small cell lung cancer are highly tumorigenic and chemoresistant but sensitive to a novel neuropeptide antagonist

Sana Sarvi, Alison C. Mackinnon, Nicolaos Avlonitis, Mark Bradley, Robert C Rintoul, Doris M Rassl, Wei Wang, Stuart J. Forbes, Christopher D. Gregory, Tariq Sethi

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Small cell lung cancer (SCLC) is a highly aggressive malignancy with poor survival rates, with initial responses nearly invariably followed by rapid recurrence of therapy-resistant disease. Drug resistance in SCLC may be attributable to the persistence of a sub-population of cancer stem-like cells (CSC) that exhibit multiple drug resistance. In this study, we characterised the expression of CD133, one important marker of CSC in other cancers, in SCLC cancer cells. CD133 expression correlated with chemoresistance and increased tumorigenicity in vitro and in vivo accompanied by increased expression of Akt/PKB and Bcl-2. CD133 expression was increased in mouse and human SCLC after chemotherapy, an observation confirmed in clinical specimens isolated longitudinally from a patient receiving chemotherapy. We discovered in CD133+ SCLC cells an increased expression of the mitogenic neuropeptide receptors for gastrin releasing peptide and arginine vasopressin. Notably, these cells exhibited increased sensitivity to the growth inhibitory and pro-apoptotic effects of a novel broad spectrum neuropeptide antagonist (related to SP-G) which has completed a Phase I clinical trial for SCLC. Our results offer evidence that this agent can preferentially target chemoresistant CD133+ cells with CSC character in SCLC, emphasizing its potential utility for improving therapy in this setting.
Original languageEnglish
Pages (from-to)1554-1565
Number of pages12
JournalCancer Research
Volume74
Issue number5
Early online date16 Jan 2014
DOIs
Publication statusPublished - Mar 2014

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