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

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 HanMin 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

Department of Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

232 Citations (Scopus)

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.

Original language	English
Pages (from-to)	77-91
Number of pages	15
Journal	Cancer Cell
Volume	26
Issue number	1
DOIs	https://doi.org/10.1016/j.ccr.2014.05.002
Publication status	Published - 2014 Jul 14

Bibliographical note

Funding 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

Oncology
Cell Biology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ccr.2014.05.002

Cite this

Pradeep, S., Kim, S. W., Wu, S. Y., Nishimura, M., Chaluvally-Raghavan, P., Miyake, T., Pecot, C. V., Kim, S. J., Choi, H. J., Bischoff, F. Z., Mayer, J. A., Huang, L., Nick, A. M., Hall, C. S., Rodriguez-Aguayo, C., Zand, B., Dalton, H. J., Arumugam, T., Lee, H. J., ... Sood, A. K. (2014). Hematogenous Metastasis of Ovarian Cancer: Rethinking Mode of Spread. Cancer Cell, 26(1), 77-91. https://doi.org/10.1016/j.ccr.2014.05.002

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 2014, 'Hematogenous Metastasis of Ovarian Cancer: Rethinking Mode of Spread', Cancer Cell, vol. 26, no. 1, pp. 77-91. https://doi.org/10.1016/j.ccr.2014.05.002

@article{7fc99d65d00f4c92b631f4276ebd09af,

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.",

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

note = "Funding 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{\textquoteright}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. ",

year = "2014",

month = jul,

day = "14",

doi = "10.1016/j.ccr.2014.05.002",

language = "English",

volume = "26",

pages = "77--91",

journal = "Cancer Cell",

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TY - JOUR

T1 - Hematogenous Metastasis of Ovarian Cancer

T2 - Rethinking Mode of Spread

AU - Pradeep, Sunila

AU - Kim, Seung W.

AU - Wu, Sherry Y.

AU - Nishimura, Masato

AU - Chaluvally-Raghavan, Pradeep

AU - Miyake, Takahito

AU - Pecot, Chad V.

AU - Kim, Sun Jin

AU - Choi, Hyun Jin

AU - Bischoff, Farideh Z.

AU - Mayer, Julie Ann

AU - Huang, Li

AU - Nick, Alpa M.

AU - Hall, Carolyn S.

AU - Rodriguez-Aguayo, Cristian

AU - Zand, Behrouz

AU - Dalton, Heather J.

AU - Arumugam, Thiruvengadam

AU - Lee, Ho Jeong

AU - Han, Hee Dong

AU - Cho, Min Soon

AU - Rupaimoole, Rajesha

AU - Mangala, Lingegowda S.

AU - Sehgal, Vasudha

AU - Oh, Sang Cheul

AU - Liu, Jinsong

AU - Lee, Ju Seog

AU - Coleman, Robert L.

AU - Ram, Prahlad

AU - Lopez-Berestein, Gabriel

AU - Fidler, Isaiah J.

AU - Sood, Anil K.

N1 - Funding 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.

PY - 2014/7/14

Y1 - 2014/7/14

N2 - 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.

AB - 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.

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DO - 10.1016/j.ccr.2014.05.002

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AN - SCOPUS:84904265681

SN - 1535-6108

VL - 26

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EP - 91

JO - Cancer Cell

JF - Cancer Cell

IS - 1

ER -

Hematogenous Metastasis of Ovarian Cancer: Rethinking Mode of Spread

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

Access to Document

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