Drug-selected human lung cancer stem cells: cytokine network, tumorigenic and metastatic properties.

PloS One
Vera LevinaAnna E Lokshin

Abstract

Cancer stem cells (CSCs) are thought to be responsible for tumor regeneration after chemotherapy, although direct confirmation of this remains forthcoming. We therefore investigated whether drug treatment could enrich and maintain CSCs and whether the high tumorogenic and metastatic abilities of CSCs were based on their marked ability to produce growth and angiogenic factors and express their cognate receptors to stimulate tumor cell proliferation and stroma formation. Treatment of lung tumor cells with doxorubicin, cisplatin, or etoposide resulted in the selection of drug surviving cells (DSCs). These cells expressed CD133, CD117, SSEA-3, TRA1-81, Oct-4, and nuclear beta-catenin and lost expression of the differentiation markers cytokeratins 8/18 (CK 8/18). DSCs were able to grow as tumor spheres, maintain self-renewal capacity, and differentiate. Differentiated progenitors lost expression of CD133, gained CK 8/18 and acquired drug sensitivity. In the presence of drugs, differentiation of DSCs was abrogated allowing propagation of cells with CSC-like characteristics. Lung DSCs demonstrated high tumorogenic and metastatic potential following inoculation into SCID mice, which supported their classification as CSCs. Luminex analy...Continue Reading

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Methods Mentioned

BETA
xenografting
FACS
dissecting
FCS
flow cytometry
Fluorescence
ubiquitination
nuclear translocation

Software Mentioned

ArrayScan
FCS Express
Target Activation BioApplication
MS Excel
ArrayScan II Data Acquisition and Data Viewer
Compartment Analysis BioApplication
Target Activation
Quattro Pro

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