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Multiplexed bioluminescence imaging of cancer cell response to hypoxia and inflammation in the caudal-artery injection model of bone metastasis during zoledronic acid treatment

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Journal of Cancer Metastasis and Treatment 2021年第1期7卷 69-80页

作者： Misa Minegishi takahiro kuchimaru Kenji Nakagawa Tatsuhiro Isozaki Satoshi Fujimori Tetsuya Kadonosono Shinae Kizaka-Kondoh School of Life Science and Technology Tokyo Institute of TechnologyKanagawa 226-8501Japan Center for Molecular Medicine Jichi Medical UniversityTochigi 329-0498Japan.

Aim:Therapeutic agents suppressing bone remodeling have been clinically approved to delay metastatic progression and skeletal-related events in patients with bone ***,therapeutic agents including zoledronic acid(ZA)are insufficient to regress established bone ***,new treatment strategies are desired,and unraveling the status of cancer cells during bone metastatic progression will help develop therapeutic ***:We developed a unique multiplexed reporter system for bioluminescent imaging(MRS-BLI)using three luciferase reporter *** system allows for the noninvasive and quantitative monitoring of tumor growth and activities of nuclear factor-kappa B(NF-κB)and hypoxia-inducible factor(HIF),which are the key transcriptional factors in response to inflammation and hypoxia,***-3/MRS-BLI,a human prostate cancer cell line that stably retains the MRS-BLI reporter genes,was applied to the caudal-artery injection model of bone metastasis to observe the status of cancer cells during bone metastasis development and ZA treatment(<1 month).Results:MRS-BLI reveals key events during the bone metastasis development:NF-κB and HIF are activated in cancer cells after migration to the bone marrow and are transiently reduced,followed by rapid activation before proliferation *** treatment suppresses the growth of metastasized cancer cells by suppressing NF-κB and HIF activities that may be indirectly induced by osteoclast ***:By visualizing the NF-κB and HIF activities of PC-3/MRS-BLI in bone,MRS-BLI has enabled new discoveries regarding the regulation of bone *** analysis of the progression of bone metastases using MRS-BLI may provide important information for developing new therapeutic strategies.

关键词： Bone metastasis multiplexed bioluminescence imaging zoledronic acid nuclear factor-kappa B hypoxia inducible factor

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ROR2 regulates the survival of murine osteosarcoma cells in lung capillaries

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Journal of Cancer Metastasis and Treatment 2020年第1期6卷 611-621页

作者： Diem Thi Phuong Tran takahiro kuchimaru Mongkol Pongsuchart Kha The Nguyen John Clyde Co Soriano Tetsuya Kadonosono Shinae Kizaka-Kondoh School of Life Science and Technology Tokyo Institute of TechnologyYokohama 226-8501Japan Center for Molecular Medicine Jichi Medical UniversityTochigi 329-0498Japan

Aim:Lung metastasis is a leading cause of death in patients with osteosarcoma(OS).No effective therapy exists that improves the five-year overall survival rate of OS patients with ***,finding novel therapeutic targets will help develop new treatment strategies for OS patients with lung ***:Based on analysis of gene expression profiles between sublines of the Dunn OS LM8 cell line with high(LM8-H)and low(LM8-L)metastatic ability,we have identified Wnt signal-related genes that play an important role in lung metastasis of *** of the genes was investigated by establishing sublines of gene knockout and assessing their metastatic ability using a mouse lung metastasis *** molecular mechanism underlying the function of the genes was further investigated by in vitro ***:We have identified that receptor tyrosine kinase-like orphan receptor 2(ROR2),a receptor of the non-canonical Wnt signaling pathway,was involved in OS cell survival in lung capillaries during ***8-H knocked out of Ror2(H/Ror2-KO)significantly reduced lung metastasis by decreasing the viability in lung capillaries 48 h after intravenous *** vitro study revealed that ROR2 increased anoikis resistance through AKT *** of ROR2 expression in H/Ror2-KO cells restored their metastatic ability and viability in lung ***:The results demonstrate a novel ROR2 function in OS lung metastasis and may inform new treatment strategies for OS patients.

关键词： Osteosarcoma lung metastasis cell survival lung capillary ROR2

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