The osteogenic niche promotes early-stage bone colonization of disseminated breast cancer cells

Hai Wang; Cuijuan Yu; Xia Gao; Thomas Welte; Aaron M Muscarella; Lin Tian; Hong Zhao; Zhen Zhao; Shiyu Du; Jianning Tao; Brendan Lee; Thomas F Westbrook; Stephen T C Wong; Xin Jin; Jeffrey M Rosen; C Kent Osborne; Xiang H-F Zhang

doi:10.1016/j.ccell.2014.11.017

The osteogenic niche promotes early-stage bone colonization of disseminated breast cancer cells

Hai Wang, Cuijuan Yu, Xia Gao, Thomas Welte, Aaron M Muscarella, Lin Tian, Hong Zhao, Zhen Zhao, Shiyu Du, Jianning Tao, Brendan Lee, Thomas F Westbrook, Stephen T C Wong, Xin Jin, Jeffrey M Rosen, C Kent Osborne, Xiang H-F Zhang

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

280 Scopus citations

Abstract

Breast cancer bone micrometastases can remain asymptomatic for years before progressing into overt lesions. The biology of this process, including the microenvironment niche and supporting pathways, is unclear. We find that bone micrometastases predominantly reside in a niche that exhibits features of osteogenesis. Niche interactions are mediated by heterotypic adherens junctions (hAJs) involving cancer-derived E-cadherin and osteogenic N-cadherin, the disruption of which abolishes niche-conferred advantages. We elucidate that hAJ activates the mTOR pathway in cancer cells, which drives the progression from single cells to micrometastases. Human data set analyses support the roles of AJ and the mTOR pathway in bone colonization. Our study illuminates the initiation of bone colonization, and provides potential therapeutic targets to block progression toward osteolytic metastases.

Original language	English (US)
Pages (from-to)	193-210
Number of pages	18
Journal	Cancer Cell
Volume	27
Issue number	2
DOIs	https://doi.org/10.1016/j.ccell.2014.11.017
State	Published - Feb 9 2015

Keywords

Bone Neoplasms
Breast Neoplasms
Cadherins
Cell Line, Tumor
Female
Humans
Neoplasm Staging
Osteogenesis
TOR Serine-Threonine Kinases
Tumor Microenvironment

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10.1016/j.ccell.2014.11.017

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Wang, H., Yu, C., Gao, X., Welte, T., Muscarella, A. M., Tian, L., Zhao, H., Zhao, Z., Du, S., Tao, J., Lee, B., Westbrook, T. F., Wong, S. T. C., Jin, X., Rosen, J. M., Osborne, C. K., & Zhang, X. H.-F. (2015). The osteogenic niche promotes early-stage bone colonization of disseminated breast cancer cells. Cancer Cell, 27(2), 193-210. https://doi.org/10.1016/j.ccell.2014.11.017

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title = "The osteogenic niche promotes early-stage bone colonization of disseminated breast cancer cells",

abstract = "Breast cancer bone micrometastases can remain asymptomatic for years before progressing into overt lesions. The biology of this process, including the microenvironment niche and supporting pathways, is unclear. We find that bone micrometastases predominantly reside in a niche that exhibits features of osteogenesis. Niche interactions are mediated by heterotypic adherens junctions (hAJs) involving cancer-derived E-cadherin and osteogenic N-cadherin, the disruption of which abolishes niche-conferred advantages. We elucidate that hAJ activates the mTOR pathway in cancer cells, which drives the progression from single cells to micrometastases. Human data set analyses support the roles of AJ and the mTOR pathway in bone colonization. Our study illuminates the initiation of bone colonization, and provides potential therapeutic targets to block progression toward osteolytic metastases.",

keywords = "Bone Neoplasms, Breast Neoplasms, Cadherins, Cell Line, Tumor, Female, Humans, Neoplasm Staging, Osteogenesis, TOR Serine-Threonine Kinases, Tumor Microenvironment",

author = "Hai Wang and Cuijuan Yu and Xia Gao and Thomas Welte and Muscarella, {Aaron M} and Lin Tian and Hong Zhao and Zhen Zhao and Shiyu Du and Jianning Tao and Brendan Lee and Westbrook, {Thomas F} and Wong, {Stephen T C} and Xin Jin and Rosen, {Jeffrey M} and Osborne, {C Kent} and Zhang, {Xiang H-F}",

year = "2015",

month = feb,

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doi = "10.1016/j.ccell.2014.11.017",

language = "English (US)",

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pages = "193--210",

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T1 - The osteogenic niche promotes early-stage bone colonization of disseminated breast cancer cells

AU - Wang, Hai

AU - Yu, Cuijuan

AU - Gao, Xia

AU - Welte, Thomas

AU - Muscarella, Aaron M

AU - Tian, Lin

AU - Zhao, Hong

AU - Zhao, Zhen

AU - Du, Shiyu

AU - Tao, Jianning

AU - Lee, Brendan

AU - Westbrook, Thomas F

AU - Wong, Stephen T C

AU - Jin, Xin

AU - Rosen, Jeffrey M

AU - Osborne, C Kent

AU - Zhang, Xiang H-F

PY - 2015/2/9

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N2 - Breast cancer bone micrometastases can remain asymptomatic for years before progressing into overt lesions. The biology of this process, including the microenvironment niche and supporting pathways, is unclear. We find that bone micrometastases predominantly reside in a niche that exhibits features of osteogenesis. Niche interactions are mediated by heterotypic adherens junctions (hAJs) involving cancer-derived E-cadherin and osteogenic N-cadherin, the disruption of which abolishes niche-conferred advantages. We elucidate that hAJ activates the mTOR pathway in cancer cells, which drives the progression from single cells to micrometastases. Human data set analyses support the roles of AJ and the mTOR pathway in bone colonization. Our study illuminates the initiation of bone colonization, and provides potential therapeutic targets to block progression toward osteolytic metastases.

AB - Breast cancer bone micrometastases can remain asymptomatic for years before progressing into overt lesions. The biology of this process, including the microenvironment niche and supporting pathways, is unclear. We find that bone micrometastases predominantly reside in a niche that exhibits features of osteogenesis. Niche interactions are mediated by heterotypic adherens junctions (hAJs) involving cancer-derived E-cadherin and osteogenic N-cadherin, the disruption of which abolishes niche-conferred advantages. We elucidate that hAJ activates the mTOR pathway in cancer cells, which drives the progression from single cells to micrometastases. Human data set analyses support the roles of AJ and the mTOR pathway in bone colonization. Our study illuminates the initiation of bone colonization, and provides potential therapeutic targets to block progression toward osteolytic metastases.

KW - Bone Neoplasms

KW - Breast Neoplasms

KW - Cadherins

KW - Cell Line, Tumor

KW - Female

KW - Humans

KW - Neoplasm Staging

KW - Osteogenesis

KW - TOR Serine-Threonine Kinases

KW - Tumor Microenvironment

U2 - 10.1016/j.ccell.2014.11.017

DO - 10.1016/j.ccell.2014.11.017

M3 - Article

C2 - 25600338

SN - 1535-6108

VL - 27

SP - 193

EP - 210

JO - Cancer Cell

JF - Cancer Cell

IS - 2

ER -

The osteogenic niche promotes early-stage bone colonization of disseminated breast cancer cells

Abstract

Keywords

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