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Molecular portraits of intratumoral heterogeneity in human ovarian c

Authors
 Yoon Pyo Choi  ;  Hyo Sup Shim  ;  Ming-Qing Gao  ;  Suki Kang  ;  Nam Hoon Cho 
Citation
 CANCER LETTERS, Vol.307(1) : 62-71, 2011 
Journal Title
CANCER LETTERS
ISSN
 0304-3835 
Issue Date
2011
MeSH
Adenosine Triphosphate/metabolism ; Antineoplastic Agents/pharmacology ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Cell Proliferation/drug effects ; Chromosome Aberrations ; Clone Cells ; Comparative Genomic Hybridization ; Female ; Gene Expression Profiling* ; Humans ; Immunophenotyping ; Middle Aged ; Neoplastic Stem Cells/drug effects ; Neoplastic Stem Cells/pathology* ; Oligonucleotide Array Sequence Analysis ; Ovarian Neoplasms/classification* ; Ovarian Neoplasms/genetics* ; Ovarian Neoplasms/pathology ; Phenotype ; RNA, Messenger/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Side-Population Cells/pathology* ; Tumor Cells, Cultured
Keywords
Human ovary cancer ; Intratumoral heterogeneity ; Cancer stem-like cell ; Side population ; Array CGH
Abstract
One of the most common characteristic profiles of cancer is intratumoral heterogeneity (ITH). We aimed to clarify the molecular profiles and biological significance of ITH with relation to cancer stem cell (CSC). We analyzed five primary cultured clones generated from different spatial zones, front and rear zone, of a fresh-frozen ovarian tumor tissue, performing ATP-CRA, conventional RT-PCR, side population (SP) analysis, flow cytometry immunophenotyping, and cell proliferation assays. We also carried out array CGH and Ingenuity Pathways Analysis (IPA) between SP and non-SP (NSP) cells. Clones from tumor front zone showed phenotypically and genetically distinct subpopulations with relatively higher SP proportions, CD24(+) and CD117(+) expression, and chemotherapeutic resistance. We demonstrate that phenotype of SP cells in heterogeneous clones of human ovarian cancer was closely related to CD24(+), CD117(+), and combined CD117(+)/CD24(+) fractions. Chromosomal alterations in SP cells relative to NSP cells were closely related to the novel core networks of cancer stem cell-like cells (CSCs), such as cycle checkpoint regulation, notch, PTEN, wnt/β-catenin, PI3K/AKT, integrin, and cytokine and chemokine signaling. ITH could arise from clonal diversity closely related to CSC-like molecules, as evidenced by accumulated genetic, transcriptional and gene products alterations in SP.
Full Text
http://www.sciencedirect.com/science/article/pii/S0304383511001686
DOI
10.1016/j.canlet.2011.03.018
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kang, Suki(강숙희) ORCID logo https://orcid.org/0000-0002-9957-3479
Shim, Hyo Sup(심효섭) ORCID logo https://orcid.org/0000-0002-5718-3624
Cho, Nam Hoon(조남훈) ORCID logo https://orcid.org/0000-0002-0045-6441
Choi, Yoon Pyo(최윤표)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/93286
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