Hematogenous metastasis of ovarian cancer: rethinking mode of spread.
Cancer Cell, 2014/7/14;26(1):77-91.
Pradeep S[1], Kim SW[2], Wu SY[1], Nishimura M[1], Chaluvally-Raghavan P[3], Miyake T[1], Pecot CV[4], Kim SJ[2], Choi HJ[1], Bischoff FZ[5], Mayer JA[5], Huang L[2], Nick AM[1], Hall CS[6], Rodriguez-Aguayo C[7], Zand B[1], Dalton HJ[1], Arumugam T[2], Lee HJ[2], Han HD[8], Cho MS[9], Rupaimoole R[1], Mangala LS[10], Sehgal V[3], Oh SC[11], Liu J[12], Lee JS[3], Coleman RL[1], Ram P[3], Lopez-Berestein G[7], Fidler IJ[2], Sood AK[13]
Affiliations
PMID: 25026212
Impact factor: 38.585
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.
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; 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
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