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.
Bibliographical noteFunding Information:
The authors thank Donna Reynolds, Dr. Robert Langley, Cristina Ivan, and Sang-Bae Kim for helpful discussions, for providing reagents, and for help with biostatistical analyses. We also thank David Aten for help with graphics. S.Y.W. is supported by Ovarian Cancer Research Fund, Inc., Foundation for Women’s Cancer, and Cancer Prevention Research Institute Texas (CPRIT) training grants (RP101502 and RP101489). B.Z. and H.J.D. are supported by NIH T32 Training Grant CA101642. P.C.R. is supported by the Ann Schreiber Program for Excellence grant from the Ovarian Cancer Research Foundation and a Scientific scholar award from the Marsha Rivkin Center for Ovarian Cancer Research. This work was also supported in part by NIH grants (P50CA083639, CA109298, P50CA098258, CA177909, U54CA151668, UH2TR000943, CA016672, U54CA96300, and U54CA96297), CPRIT RP110595 and RP120214, an Ovarian Cancer Research Fund Program Project Development Grant, Department of Defense grants (OC120547 and OC093416), the Betty Ann Asche Murray Distinguished Professorship, the Marcus Foundation, the RGK Foundation, the Gilder Foundation, the Judi A. Rees Ovarian Cancer Research Fund, the Chapman Foundation, the Meyer and Ida Gordon Foundation, the Ann Rife Cox Chair in Gynecology, and the Blanton-Davis Ovarian Cancer Research Program. We also acknowledge support from the Small Animal Imaging Facility.
ASJC Scopus subject areas
- Cell Biology
- Cancer Research