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PMID: 19158483 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Molecular phenotyping of human ovarian cancer stem cells unravels the mechanisms for repair and chemoresistance.

Cell cycle (Georgetown, Tex.) ·Vol. 8 ·No. 1 ·2009-01-01 ·Pages 158-66

Alvero AB, Chen R, Fu HH, Montagna M, Schwartz PE, Rutherford T, Silasi DA, Steffensen KD, Waldstrom M, Visintin I, Mor G

Abstract

A major burden in the treatment of ovarian cancer is the high percentage of recurrence and chemoresistance. Cancer stem cells (CSCs) provide a reservoir of cells that can self-renew, can maintain the tumor by generating differentiated cells [non-stem cells (non-CSCs)] which make up the bulk of the tumor and may be the primary source of recurrence. We describe the characterization of human ovarian cancer stem cells (OCSCs). These cells have a distinctive genetic profile that confers them with the capacity to recapitulate the original tumor, proliferate with chemotherapy, and promote recurrence. CSC identified in EOC cells isolated form ascites and solid tumors are characterized by: CD44+, MyD88+, constitutive NFkappaB activity and cytokine and chemokine production, high capacity for repair, chemoresistance to conventional chemotherapies, resistance to TNFalpha-mediated apoptosis, capacity to form spheroids in suspension, and the ability to recapitulate in vivo the original tumor. Chemotherapy eliminates the bulk of the tumor but it leaves a core of cancer cells with high capacity for repair and renewal. The molecular properties identified in these cells may explain some of the unique characteristics of CSCs that control self-renewal and drive metastasis. The identification and cloning of human OCSCs can aid in the development of better therapeutic approaches for ovarian cancer patients.

MeSH Terms
Animals Cell Differentiation Cell Proliferation Cytokines/biosynthesis Drug Resistance, Neoplasm Female Gene Expression Profiling Gene Expression Regulation, Neoplastic Humans Hyaluronan Receptors/metabolism Mice Myeloid Differentiation Factor 88/metabolism NF-kappa B/metabolism Neoplastic Stem Cells/metabolism,pathology Ovarian Neoplasms/genetics,pathology,therapy Phenotype Spheroids, Cellular/metabolism,pathology Survival Analysis Toll-Like Receptor 4/metabolism Tumor Cells, Cultured
Chemicals
Cytokines Hyaluronan Receptors Myeloid Differentiation Factor 88 NF-kappa B Toll-Like Receptor 4
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Alvero Ayesha B
Department of Obstetrics and Gynecology , Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
Chen Rui
Fu Han-Hsuan
Montagna Michele
Schwartz Peter E
Rutherford Thomas
Silasi Dan-Arin
Steffensen Karina D
Waldstrom Marianne
Visintin Irene
Mor Gil
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Article Info
Journal
Cell cycle (Georgetown, Tex.)
Abbr.
Cell Cycle
ISSN
1551-4005
DOI
10.4161/cc.8.1.7533
Published
2009-01-01
Pages
158-66
Language
English
Region
United States
NLM ID
101137841
PMCID
PMC3041590
Subset
IM
Grants
NCI NIH HHS · R01 CA127913-02 · United States
NCI NIH HHS · R01 CA127913-03 · United States
NCI NIH HHS · R01 CA118678 · United States
NCI NIH HHS · R01 CA118678-03 · United States
NCI NIH HHS · 1R01 CA 118678-01A2 · United States
NCI NIH HHS · 1R01 CA 127913-01A2 · United States
NCI NIH HHS · R01 CA127913 · United States
External Links
PubMed source DOI: 10.4161/cc.8.1.7533 PMC Full Text View journal details
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