title: Hematogenous metastasis of ovarian cancer: rethinking mode of spread.
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.
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Sunila
authors.initials: S
authors.lastname: Pradeep
authors.affiliation: Department of Cancer Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Seung W
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Sherry Y
authors.initials: SY
authors.lastname: Wu
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Masato
authors.initials: M
authors.lastname: Nishimura
authors.affiliation: Department of Systems Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Chaluvally-Raghavan
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Takahito
authors.initials: T
authors.lastname: Miyake
authors.affiliation: Department of Thoracic, Head, and Neck Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Chad V
authors.initials: CV
authors.lastname: Pecot
authors.affiliation: Department of Cancer Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Sun-Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Biocept Inc., San Diego, CA 92121, USA.
authors.forename: Farideh Z
authors.initials: FZ
authors.lastname: Bischoff
authors.affiliation: Biocept Inc., San Diego, CA 92121, USA.
authors.forename: Julie Ann
authors.initials: JA
authors.lastname: Mayer
authors.affiliation: Department of Cancer Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Alpa M
authors.initials: AM
authors.lastname: Nick
authors.affiliation: Department of Surgical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Carolyn S
authors.initials: CS
authors.lastname: Hall
authors.affiliation: 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.
authors.forename: Cristian
authors.initials: C
authors.lastname: Rodriguez-Aguayo
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Behrouz
authors.initials: B
authors.lastname: Zand
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Dalton
authors.affiliation: Department of Cancer Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Thiruvengadam
authors.initials: T
authors.lastname: Arumugam
authors.affiliation: Department of Cancer Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Ho Jeong
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Hee Dong
authors.initials: HD
authors.lastname: Han
authors.affiliation: Department of Benign Hematology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Min Soon
authors.initials: MS
authors.lastname: Cho
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Rajesha
authors.initials: R
authors.lastname: Rupaimoole
authors.affiliation: 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.
authors.forename: Lingegowda S
authors.initials: LS
authors.lastname: Mangala
authors.affiliation: Department of Systems Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Vasudha
authors.initials: V
authors.lastname: Sehgal
authors.affiliation: 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.
authors.forename: Sang Cheul
authors.initials: SC
authors.lastname: Oh
authors.affiliation: Department of Pathology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Systems Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Ju-Seog
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Coleman
authors.affiliation: Department of Systems Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Prahlad
authors.initials: P
authors.lastname: Ram
authors.affiliation: 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.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Lopez-Berestein
authors.affiliation: Department of Cancer Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Isaiah J
authors.initials: IJ
authors.lastname: Fidler
authors.affiliation: 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.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
mesh_terms: D000818:Animals; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control / Q000556:secondary*; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology*; D020890:Neuregulin-1 / Q000235:genetics / Q000378:metabolism; D009852:Omentum / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D010227:Parabiosis; D010534:Peritoneal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control; D034622:RNA Interference; D020893:Receptor, ErbB-3 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: C094131:NRG1 protein, human; D020890:Neuregulin-1; C581292:ERBB3 protein, human; D020893:Receptor, ErbB-3