Molecular portraits of intratumoral heterogeneity in human ovarian cancer

Yoon Pyo Choi, Hyo Sup Shim, Ming Qing Gao, Suki Kang, Nam Hoon Cho

Research output: Contribution to journalArticle

47 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)62-71
Number of pages10
JournalCancer Letters
Volume307
Issue number1
DOIs
Publication statusPublished - 2011 Aug 1

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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