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 language | English |
|---|---|
| Pages (from-to) | 62-71 |
| Number of pages | 10 |
| Journal | Cancer Letters |
| Volume | 307 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2011 Aug 1 |
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All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research
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Molecular portraits of intratumoral heterogeneity in human ovarian cancer. / Choi, Yoon Pyo; Shim, Hyo Sup; Gao, Ming Qing; Kang, Suki; Cho, Namhoon.
In: Cancer Letters, Vol. 307, No. 1, 01.08.2011, p. 62-71.Research output: Contribution to journal › Article
TY - JOUR
T1 - Molecular portraits of intratumoral heterogeneity in human ovarian cancer
AU - Choi, Yoon Pyo
AU - Shim, Hyo Sup
AU - Gao, Ming Qing
AU - Kang, Suki
AU - Cho, Namhoon
PY - 2011/8/1
Y1 - 2011/8/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79957480642&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79957480642&partnerID=8YFLogxK
U2 - 10.1016/j.canlet.2011.03.018
DO - 10.1016/j.canlet.2011.03.018
M3 - Article
C2 - 21481528
AN - SCOPUS:79957480642
VL - 307
SP - 62
EP - 71
JO - Cancer Letters
JF - Cancer Letters
SN - 0304-3835
IS - 1
ER -