Tumor Microenvironment of Metastasis in the Bone and Brain

Tumor metastasis occurs in a relatively organ-specific manner, and the tumor microenvironment in each organ plays important roles. Our research particularly focuses on both brain and bone metastasis of breast and prostate cancers.

We identified specific components of host cells in these organs and clarified signaling networks in cancer stem cells and microenvironmental cells, which led to discoveries of several novel therapeutic targets and small molecules for potential clinical use.

Selected publications

Okuda, H., Kobayashi, A., Xia, B., Watabe, M., Pai, S.K., Hirota, S., Xing, F., Liu, W., Pandey, P.R., Fukuda, K., Modur, V., Ghosh, A., Wilber, A., and Watabe, K. (2011) HAS2 promotes metastasis by stimulating interaction of breast cancer stem cells with macrophage and stromal cells in the bone. Cancer Res. 72, 537

Kobayashi, A., Okuda, H., Pandey, P.R., Watabe, M., Hirota, S., Pai, S.K., Xing, F., Liu, W., Fukuda, K., Chambers, C., and Watabe, K. (2011) Roles of BMP7 in dormancy and recurrence of prostate cancer stem-like cell in bone. J. Exp. Med. 208, 2641 (ISMCBBPR due to this discovery) (BMP7 was selected as “Molecule of the year in 2011”)

Xing, F., Okuda, H., Kobayashi, A., Watabe, M., Pai, S.K., Pandey, P.R., Hirota, S., Moore, B.E., Liu, W., Fukuda, K., Modur, V., Iiizumi, M., Wilber, A., Peralta, E., and Watabe, K. (2013). Reactive astrocytes promote the growth of cancer stem-like cells of metastatic breast tumor by activating Notch signaling in brain. EMBO Mol. Med. 5, 384 (cover story) (Faculty 1000)

Wu, K., Fukuda, K., Xing, F., Zhan, Y., Liu, Y., Sharma, S., Mo, Y., Pochampally, R., and Watabe, K. (2015) Cooperative roles of Cox2 and MMP1 in brain metastasis of breast cancer. J. Biol. Chem. 290, 9842

Xing F, Liu Y, Sharma S, Wu K, Chan MD, Lo HW, Carpenter RL, Metheny-Barlow LJ, Zhou X, Qasem SA, Pasche B, Watabe K (2016) Activation of the c-Met pathway mobilizes an inflammatory network in the brain microenvironment to promote brain metastasis of breast cancer. Cancer Res. 2016 Jun 30. [Epub ahead of print]

Sharma S, Xing F, Liu Y, Wu K, Said N, Pochampally R, Shiozawa Y, Balaji KC, Watabe K. Roles of SPARC in metastatic dormancy of prostate cancer in the bone. J. Biol. Chem. In press