Hematogenous metastasis of ovarian cancer: rethinking mode of spread

Sunila Pradeep; Seung W Kim; Sherry Y Wu; Masato Nishimura; Pradeep Chaluvally-Raghavan; Takahito Miyake; Chad V Pecot; Sun-Jin Kim; Hyun Jin Choi; Farideh Z Bischoff; Julie Ann Mayer; Li Huang; Alpa M Nick; Carolyn S Hall; Cristian Rodriguez-Aguayo; Behrouz Zand; Heather J Dalton; Thiruvengadam Arumugam; Ho Jeong Lee; Hee Dong Han; Min Soon Cho; Rajesha Rupaimoole; Lingegowda S Mangala; Vasudha Sehgal; Sang Cheul Oh; Jinsong Liu; Ju-Seog Lee; Robert L Coleman; Prahlad Ram; Gabriel Lopez-Berestein; Isaiah J Fidler; Anil K Sood

doi:10.1016/j.ccr.2014.05.002

Hematogenous metastasis of ovarian cancer: rethinking mode of spread

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

Authors

Sunila Pradeep¹, Seung W Kim², Sherry Y Wu¹, Masato Nishimura¹, Pradeep Chaluvally-Raghavan³, Takahito Miyake¹, Chad V Pecot⁴, Sun-Jin Kim², Hyun Jin Choi¹, Farideh Z Bischoff⁵, Julie Ann Mayer⁵, Li Huang², Alpa M Nick¹, Carolyn S Hall⁶, Cristian Rodriguez-Aguayo⁷, Behrouz Zand¹, Heather J Dalton¹, Thiruvengadam Arumugam², Ho Jeong Lee², Hee Dong Han⁸, Min Soon Cho⁹, Rajesha Rupaimoole¹, Lingegowda S Mangala¹⁰, Vasudha Sehgal³, Sang Cheul Oh¹¹, Jinsong Liu¹², Ju-Seog Lee³, Robert L Coleman¹, Prahlad Ram³, Gabriel Lopez-Berestein⁷, Isaiah J Fidler², Anil K Sood¹³

Affiliations

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: [email protected].

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.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Carcinoma, Ovarian Epithelial
Cell Line, Tumor
Cell Movement
Cell Proliferation
Female
Humans
Mice
Mice, Inbred C57BL
Mice, Nude
Neoplasm Invasiveness
Neoplasms, Glandular and Epithelial / genetics
Neoplasms, Glandular and Epithelial / metabolism
Neoplasms, Glandular and Epithelial / prevention & control
Neoplasms, Glandular and Epithelial / secondary*
Neoplastic Cells, Circulating / metabolism
Neoplastic Cells, Circulating / pathology*
Neuregulin-1 / genetics
Neuregulin-1 / metabolism
Omentum / pathology*
Ovarian Neoplasms / genetics
Ovarian Neoplasms / metabolism
Ovarian Neoplasms / pathology*
Ovarian Neoplasms / therapy
Parabiosis
Peritoneal Neoplasms / genetics
Peritoneal Neoplasms / metabolism
Peritoneal Neoplasms / pathology*
Peritoneal Neoplasms / prevention & control
RNA Interference
Receptor, ErbB-3 / genetics
Receptor, ErbB-3 / metabolism
Signal Transduction
Time Factors
Transfection
Xenograft Model Antitumor Assays

Substances

NRG1 protein, human
Neuregulin-1
ERBB3 protein, human
Receptor, ErbB-3

Abstract

Publication types

MeSH terms

Substances

Grants and funding