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Hematogenous metastasis of ovarian cancer: rethinking mode of spread. Cancer Cell 2014 Jul 14;26(1):77-91

Date

07/16/2014

Pubmed ID

25026212

Pubmed Central ID

PMC4100212

DOI

10.1016/j.ccr.2014.05.002

Scopus ID

2-s2.0-84904265681 (requires institutional sign-in at Scopus site)   262 Citations

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.

Author List

Pradeep S, Kim SW, Wu SY, Nishimura M, Chaluvally-Raghavan P, Miyake T, Pecot CV, Kim SJ, Choi HJ, Bischoff FZ, Mayer JA, Huang L, Nick AM, Hall CS, Rodriguez-Aguayo C, Zand B, Dalton HJ, Arumugam T, Lee HJ, Han HD, Cho MS, Rupaimoole R, Mangala LS, Sehgal V, Oh SC, Liu J, Lee JS, Coleman RL, Ram P, Lopez-Berestein G, Fidler IJ, Sood AK

Authors

Pradeep Chaluvally-Raghavan PhD Associate Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin
Sunila Pradeep PhD Associate Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Cell Line, Tumor
Cell Movement
Cell Proliferation
Female
Humans
Mice
Mice, Inbred C57BL
Mice, Nude
Neoplasm Invasiveness
Neoplasms, Glandular and Epithelial
Neoplastic Cells, Circulating
Neuregulin-1
Omentum
Ovarian Neoplasms
Parabiosis
Peritoneal Neoplasms
RNA Interference
Receptor, ErbB-3
Signal Transduction
Time Factors
Transfection
Xenograft Model Antitumor Assays