Specific bone region localization of osteolytic versus osteoblastic lesions in a patient-derived xenograft model of bone metastatic prostate cancer

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

Asian Journal of Urology (Oct 2016)

Specific bone region localization of osteolytic versus osteoblastic lesions in a patient-derived xenograft model of bone metastatic prostate cancer

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

Affiliations

Takeshi Hirata: Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
Seung Chol Park: Department of Urology, Wonkwang University School of Medicine and Hospital, Iksan, South Korea
Michelle T. Muldong: Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA; Department of Urology, University of California, San Diego, La Jolla, CA, USA; Department of Surgery, University of California, San Diego, La Jolla, CA, USA
Christina N. Wu: Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA; Department of Medicine, University of California, San Diego, La Jolla, CA, USA
Tomonori Yamaguchi: Department of Orthopaedic Surgery, School of Medicine, University of California, San Diego, La Jolla, CA, USA
Amy Strasner: Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA; Department of Urology, University of California, San Diego, La Jolla, CA, USA; Department of Surgery, University of California, San Diego, La Jolla, CA, USA
Omer Raheem: Department of Urology, University of California, San Diego, La Jolla, CA, USA; Department of Surgery, University of California, San Diego, La Jolla, CA, USA
Hiromi Kumon: Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
Robert L. Sah: Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA
Nicholas A. Cacalano: Department of Radiation Oncology, University of California at Los Angeles, Los Angeles, CA, USA
Catriona H.M. Jamieson: Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA; Department of Medicine, University of California, San Diego, La Jolla, CA, USA
Christopher J. Kane: Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA; Department of Urology, University of California, San Diego, La Jolla, CA, USA; Department of Surgery, University of California, San Diego, La Jolla, CA, USA
Koichi Masuda: Department of Orthopaedic Surgery, School of Medicine, University of California, San Diego, La Jolla, CA, USA
Anna A. Kulidjian: Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA; Department of Orthopaedic Surgery, School of Medicine, University of California, San Diego, La Jolla, CA, USA
Christina A.M. Jamieson: Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA; Department of Urology, University of California, San Diego, La Jolla, CA, USA; Department of Surgery, University of California, San Diego, La Jolla, CA, USA; Corresponding author. Department of Urology, Department of Surgery, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.

Journal volume & issue: Vol. 3, no. 4
pp. 229 – 239

Abstract

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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. Keywords: Bone metastatic prostate cancer, Patient-derived xenograft, Bone microenvironment, Microstructural CT, Osteolytic lesions, Osteoblastic lesions

Published in Asian Journal of Urology

ISSN: 2214-3882 (Print)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the genitourinary system. Urology
Website: http://www.journals.elsevier.com/asian-journal-of-urology

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