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Targeting CD133 in an in vivo ovarian cancer model reduces ovarian cancer progression.

Abstract：

OBJECTIVES:While most women with ovarian cancer will achieve complete remission after treatment, the majority will relapse within two years, highlighting the need for novel therapies. Cancer stem cells (CSC) have been identified in ovarian cancer and most other carcinomas as a small population of cells that can self-renew. CSC are more chemoresistant and radio-resistant than the bulk tumor cells; it is likely that CSC are responsible for relapse, the major problem in cancer treatment. CD133 has emerged as one of the most promising markers for CSC in ovarian cancer. The hypothesis driving this study is that despite their low numbers in ovarian cancer tumors, CSC can be eradicated using CD133 targeted therapy and tumor growth can be inhibited. METHODS:Ovarian cancer cell lines were evaluated using flow cytometry for expression of CD133. In vitro viability studies with an anti-CD133 targeted toxin were performed on one of the cell lines, NIH:OVCAR5. The drug was tested in vivo using a stably transfected luciferase-expressing NIH:OVCAR5 subline in nude mice, so that tumor growth could be monitored by digital imaging in real time. RESULTS:Ovarian cancer cell lines showed 5.6% to 16.0% CD133 expression. dCD133KDEL inhibited the in vitro growth of NIH:OVCAR5 cells. Despite low numbers of CD133-expressing cells in the tumor population, intraperitoneal drug therapy caused a selective decrease in tumor progression in intraperitoneal NIH:OVCAR5-luc tumors. CONCLUSIONS:Directly targeting CSC that are a major cause of drug resistant tumor relapse with an anti-CD133 targeted toxin shows promise for ovarian cancer therapy.

journal_name

Gynecol Oncol

journal_title

Gynecologic oncology

authors

Skubitz AP,Taras EP,Boylan KL,Waldron NN,Oh S,Panoskaltsis-Mortari A,Vallera DA

doi

10.1016/j.ygyno.2013.05.027

subject

Has Abstract

pub_date

2013-09-01 00:00:00

pages

579-87

issue

3

eissn

0090-8258

issn

1095-6859

pii

S0090-8258(13)00760-9

journal_volume

130

pub_type

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