TY - JOUR

T1 - Gene expression profiling of tumor-initiating stem cells from mouse Krebs-2 carcinoma using a novel marker of poorly differentiated cells

AU - Potter, Ekaterina A.

AU - Dolgova, Evgenia V.

AU - Proskurina, Anastasia S.

AU - Efremov, Yaroslav R.

AU - Minkevich, Alexandra M.

AU - Rozanov, Aleksey S.

AU - Peltek, Sergey E.

AU - Nikolin, Valeriy P.

AU - Popova, Nelly A.

AU - Seledtsov, Igor A.

AU - Molodtsov, Vladimir V.

AU - Zavyalov, Evgeniy L.

AU - Taranov, Oleg S.

AU - Baiborodin, Sergey I.

AU - Ostanin, Alexander A.

AU - Chernykh, Elena R.

AU - Kolchanov, Nikolay A.

AU - Bogachev, Sergey S.

PY - 2017/2/7

Y1 - 2017/2/7

N2 - Using the ability of poorly differentiated cells to natively internalize fragments of extracellular double-stranded DNA as a marker, we isolated a tumorigenic subpopulation present in Krebs-2 ascites that demonstrated the features of tumor-inducing cancer stem cells. Having combined TAMRA-labeled DNA probe and the power of RNA-seq technology, we identified a set of 168 genes specifically expressed in TAMRA-positive cells (tumor-initiating stem cells), these genes remaining silent in TAMRA-negative cancer cells. TAMRA+ cells displayed gene expression signatures characteristic of both stem cells and cancer cells. The observed expression differences between TAMRA+ and TAMRA- cells were validated by Real Time PCR. The results obtained corroborated the biological data that TAMRA+ murine Krebs-2 tumor cells are tumor-initiating stem cells. The approach developed can be applied to profile any poorly differentiated cell types that are capable of immanent internalization of double-stranded DNA.

AB - Using the ability of poorly differentiated cells to natively internalize fragments of extracellular double-stranded DNA as a marker, we isolated a tumorigenic subpopulation present in Krebs-2 ascites that demonstrated the features of tumor-inducing cancer stem cells. Having combined TAMRA-labeled DNA probe and the power of RNA-seq technology, we identified a set of 168 genes specifically expressed in TAMRA-positive cells (tumor-initiating stem cells), these genes remaining silent in TAMRA-negative cancer cells. TAMRA+ cells displayed gene expression signatures characteristic of both stem cells and cancer cells. The observed expression differences between TAMRA+ and TAMRA- cells were validated by Real Time PCR. The results obtained corroborated the biological data that TAMRA+ murine Krebs-2 tumor cells are tumor-initiating stem cells. The approach developed can be applied to profile any poorly differentiated cell types that are capable of immanent internalization of double-stranded DNA.

KW - DNA internalization

KW - Real Time PCR

KW - RNAseq

KW - TAMRA

KW - Tumor-initiating stem cells

KW - Gene Expression Profiling/methods

KW - Rhodamines/metabolism

KW - Signal Transduction

KW - Gene Expression Regulation, Neoplastic

KW - Neoplastic Stem Cells/metabolism

KW - Transcriptome

KW - Carcinoma, Krebs 2/genetics

KW - Gene Regulatory Networks

KW - Biomarkers, Tumor/genetics

KW - DNA/genetics

KW - Phenotype

KW - Animals

KW - Sequence Analysis, RNA

KW - Cell Differentiation

KW - High-Throughput Nucleotide Sequencing

KW - Fluorescent Dyes/metabolism

KW - Alu Elements

KW - Real-Time Polymerase Chain Reaction

KW - SIGNALING PATHWAYS

KW - COLONY-STIMULATING FACTOR

KW - DRUG-RESISTANCE

KW - BREAST-CANCER

KW - IN-VITRO

KW - tumor-initiating stem cells

KW - PROSTATE-CANCER

KW - ANTIAPOPTOTIC GENES

KW - CANCER-ASSOCIATED FIBROBLASTS

KW - SELF-RENEWAL

KW - ACUTE MYELOID-LEUKEMIA

UR - http://www.scopus.com/inward/record.url?scp=85012025889&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.14116

DO - 10.18632/oncotarget.14116

M3 - Article

C2 - 28031533

AN - SCOPUS:85012025889

VL - 8

SP - 9425

EP - 9441

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 6

ER -