Osteocyte-Driven Downregulation of Snail Restrains Effects of Drd2 Inhibitors on Mammary Tumor Cells

Cancer Research
Shengzhi LiuHiroki Yokota

Abstract

While bone is a frequent target of breast cancer-associated metastasis, little is known about the effects of tumor-bone interactions on the efficacy of tumor-suppressing agents. Here we examined the effect of two FDA-approved dopamine modulators, fluphenazine and trifluoperazine, on mammary tumor cells, osteoclasts, osteoblasts, and osteocytes. These agents suppressed proliferation and migration of mammary tumor cells chiefly by antagonizing dopamine receptor D2 and reduced bone resorption by downregulating nuclear factor of activated T cells, cytoplasmic 1 (Nfatc1). Three-dimensional spheroid formation assays revealed that tumor cells have high affinity to osteocytes and type I collagen, and interactions with osteocytes as well as administration of fluphenazine and trifluoperazine downregulated Snail and suppressed migratory behaviors. Unlike the inhibitory action of fluphenazine and trifluoperazine on tumor growth, tumor-osteocyte interactions stimulated tumor proliferation by upregulating NFκB and Akt. In the bone microenvironment, osteocytes downregulated Snail and acted as an attractant as well as a stimulant to mammary tumor cells. These results demonstrate that tumor-osteocyte interactions strengthen dopamine receptor-me...Continue Reading

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Citations

Oct 6, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Luqi WangHiroki Yokota
Aug 4, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Shengzhi LiuHiroki Yokota
May 28, 2019·Integrative Biology : Quantitative Biosciences From Nano to Macro·Xueting MeiLidan You
Nov 12, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Yong XiaLuoting Yu
Feb 6, 2021·Biomacromolecules·Han D NguyenChien-Chi Lin
Feb 10, 2021·Journal of Experimental & Clinical Cancer Research : CR·Stuart R PierceVictoria Bae-Jump
Feb 7, 2021·Bone Research·Francisco ConceiçãoMeriem Lamghari
Apr 6, 2021·Current Osteoporosis Reports·Manish Adhikari, Jesús Delgado-Calle
May 28, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Xiaofei SheZhewen Dong
Jun 3, 2021·Cancers·Nico Hinz, Manfred Jücker
Nov 14, 2021·Current Osteoporosis Reports·Fabrizio PinAndrea Bonetto

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