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Cancer Cell. 2014 Jul 14;26(1):77-91. doi: 10.1016/j.ccr.2014.05.002.

Hematogenous metastasis of ovarian cancer: rethinking mode of spread.

Author information

1
Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
2
Department of Cancer Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
3
Department of Systems Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
4
Department of Thoracic, Head, and Neck Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
5
Biocept Inc., San Diego, CA 92121, USA.
6
Department of Surgical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
7
Department of Experimental Therapeutics, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA; Center for RNA Interference and Non-coding RNA, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
8
Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA; Center for RNA Interference and Non-coding RNA, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA; Department of Immunology Laboratory, School of Medicine, Konkuk University, Chungju 380-701, South Korea.
9
Department of Benign Hematology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
10
Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA; Center for RNA Interference and Non-coding RNA, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
11
Department of Systems Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA; Division of Hemato-Oncology, Department of Internal Medicine, Korea University Medical Center, Korea University College of Medicine, Seoul 136-705, Korea.
12
Department of Pathology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
13
Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA; Department of Cancer Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA; Center for RNA Interference and Non-coding RNA, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: asood@mdanderson.org.

Abstract

Ovarian cancer has a clear predilection for metastasis to the omentum, but the underlying mechanisms involved in ovarian cancer spread are not well understood. Here, we used a parabiosis model that demonstrates preferential hematogenous metastasis of ovarian cancer to the omentum. Our studies revealed that the ErbB3-neuregulin 1 (NRG1) axis is a dominant pathway responsible for hematogenous omental metastasis. Elevated levels of ErbB3 in ovarian cancer cells and NRG1 in the omentum allowed for tumor cell localization and growth in the omentum. Depletion of ErbB3 in ovarian cancer impaired omental metastasis. Our results highlight hematogenous metastasis as an important mode of ovarian cancer metastasis. These findings have implications for designing alternative strategies aimed at preventing and treating ovarian cancer metastasis.

PMID:
25026212
PMCID:
PMC4100212
DOI:
10.1016/j.ccr.2014.05.002
[Indexed for MEDLINE]
Free PMC Article

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