Specific bone region localization of osteolytic versus osteoblastic lesions in a patient-derived xenograft model of bone metastatic prostate cancer
Takeshi Hirataa, Seung Chol Parkb, Michelle T. Muldongc,d,e, Christina N. Wuc,f, Tomonori Yamaguchig, Amy Strasnerc,d,e, Omer Raheemd,e, Hiromi Kumona, Robert L. Sahh, Nicholas A. Cacalanoi, Catriona H. M. Jamiesonc,f, Christopher J. Kanec,d,e, Koichi Masudag, Anna A. Kulidjianc,g, Christina A. M. Jamiesonc,d,e
a Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; b Department of Urology, Wonkwang University School of Medicine and Hospital, Iksan, South Korea; c Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA; d Department of Urology, University of California, San Diego, La Jolla, CA, USA; e Department of Surgery, University of California, San Diego, La Jolla, CA, USA; f Department of Medicine, University of California, San Diego, La Jolla, CA, USA; g Department of Orthopaedic Surgery, School of Medicine, University of California, San Diego, La Jolla, CA, USA; h Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA; i Department of Radiation Oncology, University of California at Los Angeles, Los Angeles, CA, USA
Specific bone region localization of osteolytic versus osteoblastic lesions in a patient-derived xenograft model of bone metastatic prostate cancer
Takeshi Hirataa, Seung Chol Parkb, Michelle T. Muldongc,d,e, Christina N. Wuc,f, Tomonori Yamaguchig, Amy Strasnerc,d,e, Omer Raheemd,e, Hiromi Kumona, Robert L. Sahh, Nicholas A. Cacalanoi, Catriona H. M. Jamiesonc,f, Christopher J. Kanec,d,e, Koichi Masudag, Anna A. Kulidjianc,g, Christina A. M. Jamiesonc,d,e
a Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; b Department of Urology, Wonkwang University School of Medicine and Hospital, Iksan, South Korea; c Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA; d Department of Urology, University of California, San Diego, La Jolla, CA, USA; e Department of Surgery, University of California, San Diego, La Jolla, CA, USA; f Department of Medicine, University of California, San Diego, La Jolla, CA, USA; g Department of Orthopaedic Surgery, School of Medicine, University of California, San Diego, La Jolla, CA, USA; h Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA; i Department of Radiation Oncology, University of California at Los Angeles, Los Angeles, CA, USA
摘要 Objective: Bone metastasis occurs in up to 90% of men with advanced prostate cancer and leads to fractures, severe pain and therapy-resistance. Bone metastases induce a spectrum of types of bone lesions which can respond differently to therapy even within individual prostate cancer patients. Thus, the special environment of the bone makes the disease more complicated and incurable. A model in which bone lesions are reproducibly induced that mirrors the complexity seen in patients would be invaluable for pre-clinical testing of novel treatments. The microstructural changes in the femurs of mice implanted with PCSD1, a new patient-derived xenograft from a surgical prostate cancer bone metastasis specimen, were determined. Methods: Quantitative micro-computed tomography (micro-CT) and histological analyses were performed to evaluate the effects of direct injection of PCSD1 cells or media alone (Control) into the right femurs of Rag2-/-γc-/- male mice. Results: Bone lesions formed only in femurs of mice injected with PCSD1 cells. Bone volume (BV) was significantly decreased at the proximal and distal ends of the femurs (p<0.01) whereas BV (p<0.05) and bone shaft diameter (p<0.01) were significantly increased along the femur shaft. Conclusion: PCSD1 cells reproducibly induced bone loss leading to osteolytic lesions at the ends of the femur, and, in contrast, induced aberrant bone formation leading to osteoblastic lesions along the femur shaft. Therefore, the interaction of PCSD1 cells with different bone region-specific microenvironments specified the type of bone lesion. Our approach can be used to determine if different bone regions support more therapy resistant tumor growth, thus, requiring novel treatments.
Abstract: Objective: Bone metastasis occurs in up to 90% of men with advanced prostate cancer and leads to fractures, severe pain and therapy-resistance. Bone metastases induce a spectrum of types of bone lesions which can respond differently to therapy even within individual prostate cancer patients. Thus, the special environment of the bone makes the disease more complicated and incurable. A model in which bone lesions are reproducibly induced that mirrors the complexity seen in patients would be invaluable for pre-clinical testing of novel treatments. The microstructural changes in the femurs of mice implanted with PCSD1, a new patient-derived xenograft from a surgical prostate cancer bone metastasis specimen, were determined. Methods: Quantitative micro-computed tomography (micro-CT) and histological analyses were performed to evaluate the effects of direct injection of PCSD1 cells or media alone (Control) into the right femurs of Rag2-/-γc-/- male mice. Results: Bone lesions formed only in femurs of mice injected with PCSD1 cells. Bone volume (BV) was significantly decreased at the proximal and distal ends of the femurs (p<0.01) whereas BV (p<0.05) and bone shaft diameter (p<0.01) were significantly increased along the femur shaft. Conclusion: PCSD1 cells reproducibly induced bone loss leading to osteolytic lesions at the ends of the femur, and, in contrast, induced aberrant bone formation leading to osteoblastic lesions along the femur shaft. Therefore, the interaction of PCSD1 cells with different bone region-specific microenvironments specified the type of bone lesion. Our approach can be used to determine if different bone regions support more therapy resistant tumor growth, thus, requiring novel treatments.
通讯作者:
Christina A.M. Jamieson,E-mail address: camjamieson@ucsd.edu
E-mail: camjamieson@ucsd.edu
引用本文:
Takeshi Hirata, Seung Chol Park, Michelle T. Muldong, Christina N. Wu, Tomonori Yamaguchi, Amy Strasner, Omer Raheem, Hiromi Kumon, Robert L. Sah, Nicholas A. Cacalano, Catriona H. M. Jamieson, Christopher J. Kane, Koichi Masuda, Anna A. Kulidjian, Christina A. M. Jamieson. Specific bone region localization of osteolytic versus osteoblastic lesions in a patient-derived xenograft model of bone metastatic prostate cancer[J]. Asian Journal of Urology, 2016, 3(4): 229-239.
Takeshi Hirata, Seung Chol Park, Michelle T. Muldong, Christina N. Wu, Tomonori Yamaguchi, Amy Strasner, Omer Raheem, Hiromi Kumon, Robert L. Sah, Nicholas A. Cacalano, Catriona H. M. Jamieson, Christopher J. Kane, Koichi Masuda, Anna A. Kulidjian, Christina A. M. Jamieson. Specific bone region localization of osteolytic versus osteoblastic lesions in a patient-derived xenograft model of bone metastatic prostate cancer. Asian Journal of Urology, 2016, 3(4): 229-239.
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