The role of S100A4 for bone metastasis in prostate cancer cells
Abstract Background Prostate cancers frequently metastasize to bone, where the best microenvironment for distant colonization is provided. Since osteotropic metastasis of prostate cancer is a critical determinant of patients’ survival, searches for preventive measures are ongoing in the field. There...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-02-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-021-07850-4 |
| _version_ | 1818623199490867200 |
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| author | Bongjun Kim Suhan Jung Haemin Kim Jun-Oh Kwon Min-Kyoung Song Min Kyung Kim Hyung Joon Kim Hong-Hee Kim |
| author_facet | Bongjun Kim Suhan Jung Haemin Kim Jun-Oh Kwon Min-Kyoung Song Min Kyung Kim Hyung Joon Kim Hong-Hee Kim |
| author_sort | Bongjun Kim |
| collection | DOAJ |
| description | Abstract Background Prostate cancers frequently metastasize to bone, where the best microenvironment for distant colonization is provided. Since osteotropic metastasis of prostate cancer is a critical determinant of patients’ survival, searches for preventive measures are ongoing in the field. Therefore, it is important to dissect the mechanisms of each step of bone metastasis, including the epithelial-mesenchymal transition (EMT) and cross-talk between metastatic niches and cancer cells. Methods In this study, we established a highly bone-metastatic subline of human prostate cancer cells by selecting bone-homing population of PC3 cells after cardiac injection of eight-week-old male BALB/c-nude mice. Then we assessed the proliferation, EMT characteristics, and migration properties of the subline (mtPC3) cells in comparison with the parental PC3 cells. To investigate the role of S100A4, we performed gene knock-down by lentiviral transduction, or treated cells with recombinant S100A4 protein or a S100A4-neutralizing antibody. The effect of cancer cells on osteoclastogenesis was evaluated after treatment of pre-osteoclasts with conditioned medium (CM) from cancer cells. Results The mtPC3 cells secreted a markedly high level of S100A4 protein and showed elevated cell proliferation and mesenchymal properties. The increased proliferation and EMT traits of mtPC3 cells was inhibited by S100A4 knock-down, but was not affected by exogenous S100A4. Furthermore, S100A4 released from mtPC3 cells stimulated osteoclast development via the cell surface receptor RAGE. Down-regulation or neutralization of S100A4 in the CM of mtPC3 cells attenuated cancer-induced osteoclastogenesis. Conclusion Altogether, our results suggest that intracellular S100A4 promotes cell proliferation and EMT characteristics in tumor cells, and that secreted S100A4 activates osteoclastogenesis, contributing to osteolytic bone metastasis. Thus, S100A4 upregulation in cancer cells highly metastatic to bone might be a key element in regulating bone metastasis. |
| first_indexed | 2024-12-16T18:37:16Z |
| format | Article |
| id | doaj.art-6249fb7df8224bc4b5c1fd278ef86268 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-16T18:37:16Z |
| publishDate | 2021-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-6249fb7df8224bc4b5c1fd278ef862682022-12-21T22:21:08ZengBMCBMC Cancer1471-24072021-02-0121111310.1186/s12885-021-07850-4The role of S100A4 for bone metastasis in prostate cancer cellsBongjun Kim0Suhan Jung1Haemin Kim2Jun-Oh Kwon3Min-Kyoung Song4Min Kyung Kim5Hyung Joon Kim6Hong-Hee Kim7Department of Cell and Developmental Biology, BK21 PLUS Program and DRI, School of Dentistry, Seoul National UniversityDepartment of Cell and Developmental Biology, BK21 PLUS Program and DRI, School of Dentistry, Seoul National UniversityArthritis and Tissue Degeneration Program, David Z. Rosensweig Genomics Research Center, Hospital for Special SurgeryDepartment of Cell and Developmental Biology, BK21 PLUS Program and DRI, School of Dentistry, Seoul National UniversityDepartment of Cell and Developmental Biology, BK21 PLUS Program and DRI, School of Dentistry, Seoul National UniversityDepartment of Cell and Developmental Biology, BK21 PLUS Program and DRI, School of Dentistry, Seoul National UniversityDepartment of Oral Physiology, BK21 PLUS Project, and Dental and Life Science Institute, School of Dentistry, Pusan National UniversityDepartment of Cell and Developmental Biology, BK21 PLUS Program and DRI, School of Dentistry, Seoul National UniversityAbstract Background Prostate cancers frequently metastasize to bone, where the best microenvironment for distant colonization is provided. Since osteotropic metastasis of prostate cancer is a critical determinant of patients’ survival, searches for preventive measures are ongoing in the field. Therefore, it is important to dissect the mechanisms of each step of bone metastasis, including the epithelial-mesenchymal transition (EMT) and cross-talk between metastatic niches and cancer cells. Methods In this study, we established a highly bone-metastatic subline of human prostate cancer cells by selecting bone-homing population of PC3 cells after cardiac injection of eight-week-old male BALB/c-nude mice. Then we assessed the proliferation, EMT characteristics, and migration properties of the subline (mtPC3) cells in comparison with the parental PC3 cells. To investigate the role of S100A4, we performed gene knock-down by lentiviral transduction, or treated cells with recombinant S100A4 protein or a S100A4-neutralizing antibody. The effect of cancer cells on osteoclastogenesis was evaluated after treatment of pre-osteoclasts with conditioned medium (CM) from cancer cells. Results The mtPC3 cells secreted a markedly high level of S100A4 protein and showed elevated cell proliferation and mesenchymal properties. The increased proliferation and EMT traits of mtPC3 cells was inhibited by S100A4 knock-down, but was not affected by exogenous S100A4. Furthermore, S100A4 released from mtPC3 cells stimulated osteoclast development via the cell surface receptor RAGE. Down-regulation or neutralization of S100A4 in the CM of mtPC3 cells attenuated cancer-induced osteoclastogenesis. Conclusion Altogether, our results suggest that intracellular S100A4 promotes cell proliferation and EMT characteristics in tumor cells, and that secreted S100A4 activates osteoclastogenesis, contributing to osteolytic bone metastasis. Thus, S100A4 upregulation in cancer cells highly metastatic to bone might be a key element in regulating bone metastasis.https://doi.org/10.1186/s12885-021-07850-4Prostate cancerBone metastasisS100A4Epithelial-mesenchymal transitionOsteoclast |
| spellingShingle | Bongjun Kim Suhan Jung Haemin Kim Jun-Oh Kwon Min-Kyoung Song Min Kyung Kim Hyung Joon Kim Hong-Hee Kim The role of S100A4 for bone metastasis in prostate cancer cells BMC Cancer Prostate cancer Bone metastasis S100A4 Epithelial-mesenchymal transition Osteoclast |
| title | The role of S100A4 for bone metastasis in prostate cancer cells |
| title_full | The role of S100A4 for bone metastasis in prostate cancer cells |
| title_fullStr | The role of S100A4 for bone metastasis in prostate cancer cells |
| title_full_unstemmed | The role of S100A4 for bone metastasis in prostate cancer cells |
| title_short | The role of S100A4 for bone metastasis in prostate cancer cells |
| title_sort | role of s100a4 for bone metastasis in prostate cancer cells |
| topic | Prostate cancer Bone metastasis S100A4 Epithelial-mesenchymal transition Osteoclast |
| url | https://doi.org/10.1186/s12885-021-07850-4 |
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