Number of the records: 1
Transcriptional profiling of dividing tumor cells detects intratumor heterogeneity linked to cell proliferation in a brain tumor model
- 1.
SYSNO ASEP 0459262 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Transcriptional profiling of dividing tumor cells detects intratumor heterogeneity linked to cell proliferation in a brain tumor model Author(s) Endaya, B. (AU)
Lam, P.Y.P. (SG)
Meedeniya, A.C.B. (AU)
Neužil, Jiří (BTO-N) RIDSource Title Molecular Oncology. - : Wiley - ISSN 1574-7891
Roč. 10, č. 1 (2016), s. 126-137Number of pages 12 s. Language eng - English Country NL - Netherlands Keywords Intratumor heterogeneity ; Click chemistry ; Proliferation ; Gene profiling Subject RIV FD - Oncology ; Hematology R&D Projects ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Institutional support BTO-N - RVO:86652036 UT WOS 000369560300009 DOI 10.1016/j.molonc.2015.09.001 Annotation Intratumor heterogeneity is a primary feature of high-grade gliomas, complicating their therapy. As accumulating evidence suggests that intratumor heterogeneity is a consequence of cellular subsets with different cycling frequencies, we developed a method for transcriptional profiling of gliomas, using a novel technique to dissect the tumors into two fundamental cellular subsets, namely, the proliferating and non-proliferating cell fractions. The tumor fractions were sorted whilst maintaining their molecular integrity, by incorporating the thymidine analog 5-ethynyl-2'-deoxyuridine into actively dividing cells. We sorted the actively dividing versus non-dividing cells from cultured glioma cells, and parental and clonally derived orthotopic tumors, and analyzed them for a number of transcripts. While there was no significant difference in the transcriptional profiles between the two cellular subsets in cultured glioma cells, we demonstrate similar to 2-6 fold increase in transcripts of cancer and neuronal stem cell and tumor cell migration/invasion markers, and similar to 2-fold decrease in transcripts of markers of hypoxia and their target genes, in the dividing tumor cells of the orthotopic glioma when compared to their non-proliferative counterparts. This suggests the influence of the brain microenvironment in transcriptional regulation and, thereby, the physiology of glioma cells in vivo. When clonal glioma cells were derived from a parental glioma and the resultant orthotopic tumors were compared, their transcriptional profiles were closely correlated to tumor aggression and consequently, survival of the experimental animals. This study demonstrates the resolution of intratumor heterogeneity for profiling studies based on cell proliferation, a defining feature of cancers, with implications for treatment design. Workplace Institute of Biotechnology Contact Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Year of Publishing 2017
Number of the records: 1