Article (Scientific journals)
What Do We Learn from Spheroid Culture Systems? Insights from Tumorspheres Derived from Primary Colon Cancer Tissue.
Baig, Komal; Ullmann, Pit; Rodriguez, Fabien et al.
2016In PLoS ONE, 11
Peer Reviewed verified by ORBi
 

Files


Full Text
Qureshi-Baig_2016_Plos One.PDF
Publisher postprint (5.17 MB)
Download

All documents in ORBilu are protected by a user license.

Send to



Details



Keywords :
cancer stem cells; primary cultures; chemoresistance and plasticity
Abstract :
[en] Due to their self-renewal and tumorigenic properties, tumor-initiating cells (TICs) have been hypothesized to be important targets for colorectal cancer (CRC). However the study of TICs is hampered by the fact that the identification and culturing of TICs is still a subject of extensive debate. Floating three-dimensional spheroid cultures (SC) that grow in serum-free medium supplemented with growth factors are supposed to be enriched in TICs. We generated SC from fresh clinical tumor specimens and compared them to SC isolated from CRC cell-lines as well as to adherent differentiated counterparts. Patient-derived SC display self-renewal capacity and can induce serial transplantable tumors in immuno-deficient mice, which phenotypically resemble the tumor of origin. In addition, the original tumor tissue and established SC retain several similar CRC-relevant mutations. Primary SC express key stemness proteins such as SOX2, OCT4, NANOG and LGR5 and importantly show increased chemoresistance ability compared to their adherent differentiated counterparts and to cell line-derived SC. Strikingly, cells derived from spheroid or adherent differentiating culture conditions displayed similar self-renewal capacity and equally formed tumors in immune-deficient mice, suggesting that self-renewal and tumor-initiation capacity of TICs is not restricted to phenotypically immature spheroid cells, which we describe to be highly plastic and able to reacquire stem-cell traits even after long differentiation processes. Finally, we identified two genes among a sphere gene expression signature that predict disease relapse in CRC patients. Here we propose that SC derived from fresh patient tumor tissue present interesting phenotypic features that may have clinical relevance for chemoresistance and disease relapse and therefore represent a valuable tool to test for new CRC-therapies that overcome drug resistance.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Baig, Komal ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Ullmann, Pit ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Rodriguez, Fabien ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Frasquilho, Sonia;  Integrated Biobank of Luxembourg,
Nazarov, Petr V.;  Luxembourg Institute of Health - LIH > Genomics Research Unit
Haan, Serge ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Letellier, Elisabeth ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
External co-authors :
no
Language :
English
Title :
What Do We Learn from Spheroid Culture Systems? Insights from Tumorspheres Derived from Primary Colon Cancer Tissue.
Publication date :
January 2016
Journal title :
PLoS ONE
ISSN :
1932-6203
Publisher :
Public Library of Science, San Franscisco, United States - California
Volume :
11
Peer reviewed :
Peer Reviewed verified by ORBi
Focus Area :
Systems Biomedicine
FnR Project :
FNR7855578 - Identification And Functional Investigation Of Hypoxia-induced Mirnas In Colon Cancer Stem Cells, 2014 (01/03/2014-31/05/2017) - Pit Ullmann
Funders :
Fondation Cancer
the IntegratedBiobank of Luxembourg (IBBL)
Fondation Pélican de Mie
Available on ORBilu :
since 30 April 2016

Statistics


Number of views
179 (38 by Unilu)
Number of downloads
111 (9 by Unilu)

Scopus citations®
 
46
Scopus citations®
without self-citations
35
WoS citations
 
37

Bibliography


Similar publications



Contact ORBilu