Using a series of unique models, we discovered the initial colonization of disseminated cancer cells requires the microenvironment niche comprised of cells of the osteoblast lineage. The cancer-niche interaction is mediated by heterotypic adherens and gap junctions, which activates the mTOR and calcium pathways in cancer cells to drive progression from single cells to multi-cell micrometastases. The cancer-niche interactions also render cancer cells more stem-like and capable for further dissemination to other organs. These studies advanced our understanding of bone metastasis and revealed potential therapeutic targets.

Selected Publications

Bone metastasis initiation is coupled with bone remodeling through osteogenic differentiation of NG2+ cells
Zhang, W., Xu Z., Hao, X., He, T., Li, J., Shen, Y., Liu, K., Gao, Y., Liu, J., Edwards, D., Muscarella, A., Wu, L., Yu, L., Xu, L., Chen, X., Wu, YH., Bado, I., Ding, Y., Aguirre, S., Wang, H., Gugala, Z., Satcher, R., Wong, S., Xiang H.-F. Zhang. (Nov 21, 2022) Cancer Discovery CD-22-0220.. [DOI] [PubMed]

Bone-in-culture array as a platform to model early-stage bone metastases and discover anti-metastasis therapies
Hai Wang, Lin Tian, Jun Liu, Amit Goldstein, Igor Bado, Weijie Zhang, Benjamin R. Arenkiel, , Zonghai Li, Meng Yang, Shiyu Du, Hong Zhao, David R. Rowley, Stephen T. C. Wong, Zbigniew Gugala, Xiang H.-F. Zhang. (Apr 21, 2017) Nature Communication 258:45:00. [DOI]

Harnessing the power of antibodies to fight bone metastasis
Tian, Z., Wu, L., Yu, C., Chen, Y., Xu, Z., Bado, I., Loredo, A., Wang, L., Wang, H., Wu, K. L., Zhang, W., Xiang H.-F. Zhang & Xiao, H. (Jun 23, 2021) Science Advances Vol 7(26). [DOI]

The bone microenvironment increases phenotypic plasticity of ER+ breast cancer cells
Bado IL, Zhang W, Hu J, Xu Z, Wang H, Sarkar P, Li L, Wan YW, Liu J, Wu W, Lo HC, Kim IS, Singh S, Janghorban M, Muscarella AM, Goldstein A, Singh P, Jeong HH, Liu C, Schiff R, Huang S, Ellis MJ, Gaber MW, Gugala Z, Liu Z, Xiang H.-F. Zhang. (Apr 19, 2021) Developmental Cell 56(8):1100-1117.e9. [DOI]

The bone microenvironment invigorates metastatic seeds for further dissemination
Zhang W, Bado IL, Hu J, Wan YW, Wu L, Wang H, Gao Y, Jeong HH, Xu Z, Hao X, Lege BM, Al-Ouran R, Li L, Li J, Yu L, Singh S, Lo HC, Niu M, Liu J, Jiang W, Li Y, Wong STC, Cheng C, Liu Z, Xiang H.-F. Zhang. (Apr 29, 2021) Cell 184(9):2471-2486.e20. [DOI]

The osteogenic niche is a calcium reservoir of breast cancer bone micrometastases and confers unexpected therapeutic vulnerability
Hai Wang, Lin Tian, Jun Liu, Amit Goldstein, Igor Bado, Weijie Zhang, Benjamin R. Arenkiel, , Zonghai Li, Meng Yang, Shiyu Du, Hong Zhao, David R. Rowley, Stephen T. C. Wong, Zbigniew Gugala, Xiang H.-F. Zhang. (Nov 12, 2018) Cancer Cell 34, 823–839. [DOI]

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; Jun Liu; Hong Zhao; Zhen Zhao; Jianning Tao; Brendan Lee; Thomas F. Westbrook; Stephen T.C. Wong; Jeffrey M. Rosen; C. Kent Osborne; Xiang H.-F. Zhang. (Feb 09, 2015) Cancer Cell 27(2):193-210. [DOI]

Unique cellular protrusions mediate breast cancer cell migration by tethering to osteogenic cells
Aaron M. Muscarella, Wei Dai, Patrick G. Mitchell, Weijie Zhang, Hai Wang, Luyu Jia, Fabio Stossi, Michael A. Mancini, Wah Chiu & Xiang H.-F. Zhang. (Sep 07, 2020) npj Breast Cancer 6, 42. [DOI]