Therapeutic and Preventive Effects of Osteoclastogenesis Inhibitory Factor on Osteolysis, Proliferation of Mammary Tumor Cell and Induction of Cancer Stem Cells in the Bone Microenvironment
Autor: | Katsumi Fukamachi, Harutoshi Matsumoto, Masumi Suzui, Takao Nitanda, Saeko Ando, Mitsuru Futakuchi, Eri Yoshimoto |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Osteolysis medicine.medical_treatment Cell lcsh:Chemistry osteoclastogenesis inhibitory factor Mice 0302 clinical medicine Tumor Microenvironment Medicine Neoplasm Metastasis lcsh:QH301-705.5 Spectroscopy bone metastasis Mice Inbred BALB C Mammary tumor biology RANKL Bone metastasis General Medicine Recombinant Proteins Computer Science Applications medicine.anatomical_structure Cytokine 030220 oncology & carcinogenesis Neoplastic Stem Cells Cytokines Female bone microenvironment cancer stem cell mammary tumor Bone Neoplasms Article Catalysis Inorganic Chemistry 03 medical and health sciences Cancer stem cell Cell Line Tumor Animals Humans Physical and Theoretical Chemistry Molecular Biology Cell Proliferation Dose-Response Relationship Drug business.industry Cell growth Organic Chemistry Osteoprotegerin Mammary Neoplasms Experimental medicine.disease 030104 developmental biology lcsh:Biology (General) lcsh:QD1-999 Cancer research biology.protein business |
Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 19, Iss 3, p 888 (2018) International Journal of Molecular Sciences; Volume 19; Issue 3; Pages: 888 |
ISSN: | 1661-6596 |
Popis: | We examined the effects of recombinant human osteoclastogenesis inhibitory factor (hOCIF) on osteolysis, proliferation of mammary tumor cells, and induction of cancer stem cells (CSCs) in the tumor-bone and tumor-subcutaneous microenvironments (TB- and TS-microE). Methods: Mouse mammary tumor cells were transplanted onto the calvaria or into a subcutaneous lesion of female mice, creating a TB-microE and a TS-microE, and the mice were then treated with hOCIF. To investigate the preventive effects of hOCIF, mice were treated with hOCIF before tumor cell implantation onto the calvaria (Pre), after (Post), and both before and after (Whole). The number of CSCs and cytokine levels were evaluated by IHC and ELISA assay, respectively. Results: hOCIF suppressed osteolysis, and growth of mammary tumors in the TB-microE, but not in the TS-microE. In the Pre, Post, and Whole groups, hOCIF suppressed osteolysis, and cell proliferation. hOCIF increased mouse osteoprotegrin (mOPG) levels in vivo, which suppressed mammary tumor cell proliferation in vitro. These preventive effects were observed in the dose-dependent. hOCIF did not affect the induction of CSCs in either microenvironment. Conclusion: While receptor activator of NF-κB ligand (RANKL) targeting therapy may not affect the induction of CSCs, RANKL is a potential target for prevention as well as treatment of breast cancer bone metastasis. International Journal of Molecular Sciences, 19(3), 888; 2018 |
Databáze: | OpenAIRE |
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