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Osteoprotegerin/osteoclastogenesis inhibitory factor decreases human prostate cancer burden in human adult bone implanted into nonobese diabetic/severe combined immunodeficient mice.
Cancer Res. 2003 May 01; 63(9):2096-102.CR

Abstract

Human prostate cancer frequently metastasizes to bone, where it gives rise to osteoblastic bone metastases with an underlying osteoclastic component and subsequent bone pain. However, the importance of osteoclastogenesis in the development of prostate cancer bone lesions in humans is unclear. Osteoprotegerin/osteoclastogenesis inhibitory factor (OCIF) is a member of the tumor necrosis factor receptor family and a novel secreted protein, and it is a negative regulator of osteoclast differentiation, activation, and survival both in vitro and in vivo. In the present study we used a model in which human LNCaP prostate cancer cells that give rise to osteoblastic bone tumors were injected directly into the intramedullary space of human adult bone implanted into nonobese diabetic/severe combined immunodeficient mice to investigate whether the new bone-resorption inhibitor osteoprotegerin/OCIF would inhibit the development of new bone tumors and the progression of established osteoblastic bone tumors. The mice were given consecutive daily s.c. injections of recombinant human OCIF (rhOCIF; 100 micro g/mouse/day) for 2 weeks starting either immediately or 2 weeks after injection of the LNCaP cells. In both protocols, rhOCIF markedly inhibited both the development of bone tumors and the progression of established bone tumor foci quantified by histological examination. Histomorphometrical analysis revealed that rhOCIF markedly reduced the number of osteoclasts and the size of the tumors at the bone sites, but that it had no effect on the local growth of s.c. LNCaP tumors or on LNCaP cell proliferation in culture. These findings demonstrate that osteoclasts play an important role in bone tumor by prostate cancer, and that rhOCIF decreases the LNCaP prostate cancer burden selectively in bone, suppresses the progression of established tumor lesions, and prevents the development of new lesions. These results suggest that inhibition of osteoclastic bone resorption may be an effective therapy for the treatment of prostate cancer that has colonized bone.

Authors+Show Affiliations

Pathology Division, National Cancer Center Research Institute East, Chiba 277-8577, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12727825

Citation

Yonou, Hiroyuki, et al. "Osteoprotegerin/osteoclastogenesis Inhibitory Factor Decreases Human Prostate Cancer Burden in Human Adult Bone Implanted Into Nonobese Diabetic/severe Combined Immunodeficient Mice." Cancer Research, vol. 63, no. 9, 2003, pp. 2096-102.
Yonou H, Kanomata N, Goya M, et al. Osteoprotegerin/osteoclastogenesis inhibitory factor decreases human prostate cancer burden in human adult bone implanted into nonobese diabetic/severe combined immunodeficient mice. Cancer Res. 2003;63(9):2096-102.
Yonou, H., Kanomata, N., Goya, M., Kamijo, T., Yokose, T., Hasebe, T., Nagai, K., Hatano, T., Ogawa, Y., & Ochiai, A. (2003). Osteoprotegerin/osteoclastogenesis inhibitory factor decreases human prostate cancer burden in human adult bone implanted into nonobese diabetic/severe combined immunodeficient mice. Cancer Research, 63(9), 2096-102.
Yonou H, et al. Osteoprotegerin/osteoclastogenesis Inhibitory Factor Decreases Human Prostate Cancer Burden in Human Adult Bone Implanted Into Nonobese Diabetic/severe Combined Immunodeficient Mice. Cancer Res. 2003 May 1;63(9):2096-102. PubMed PMID: 12727825.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Osteoprotegerin/osteoclastogenesis inhibitory factor decreases human prostate cancer burden in human adult bone implanted into nonobese diabetic/severe combined immunodeficient mice. AU - Yonou,Hiroyuki, AU - Kanomata,Naoki, AU - Goya,Masato, AU - Kamijo,Tomoyuki, AU - Yokose,Tomoyuki, AU - Hasebe,Takahiro, AU - Nagai,Kanji, AU - Hatano,Tadashi, AU - Ogawa,Yoshihide, AU - Ochiai,Atsushi, PY - 2003/5/3/pubmed PY - 2003/6/17/medline PY - 2003/5/3/entrez SP - 2096 EP - 102 JF - Cancer research JO - Cancer Res VL - 63 IS - 9 N2 - Human prostate cancer frequently metastasizes to bone, where it gives rise to osteoblastic bone metastases with an underlying osteoclastic component and subsequent bone pain. However, the importance of osteoclastogenesis in the development of prostate cancer bone lesions in humans is unclear. Osteoprotegerin/osteoclastogenesis inhibitory factor (OCIF) is a member of the tumor necrosis factor receptor family and a novel secreted protein, and it is a negative regulator of osteoclast differentiation, activation, and survival both in vitro and in vivo. In the present study we used a model in which human LNCaP prostate cancer cells that give rise to osteoblastic bone tumors were injected directly into the intramedullary space of human adult bone implanted into nonobese diabetic/severe combined immunodeficient mice to investigate whether the new bone-resorption inhibitor osteoprotegerin/OCIF would inhibit the development of new bone tumors and the progression of established osteoblastic bone tumors. The mice were given consecutive daily s.c. injections of recombinant human OCIF (rhOCIF; 100 micro g/mouse/day) for 2 weeks starting either immediately or 2 weeks after injection of the LNCaP cells. In both protocols, rhOCIF markedly inhibited both the development of bone tumors and the progression of established bone tumor foci quantified by histological examination. Histomorphometrical analysis revealed that rhOCIF markedly reduced the number of osteoclasts and the size of the tumors at the bone sites, but that it had no effect on the local growth of s.c. LNCaP tumors or on LNCaP cell proliferation in culture. These findings demonstrate that osteoclasts play an important role in bone tumor by prostate cancer, and that rhOCIF decreases the LNCaP prostate cancer burden selectively in bone, suppresses the progression of established tumor lesions, and prevents the development of new lesions. These results suggest that inhibition of osteoclastic bone resorption may be an effective therapy for the treatment of prostate cancer that has colonized bone. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/12727825/Osteoprotegerin/osteoclastogenesis_inhibitory_factor_decreases_human_prostate_cancer_burden_in_human_adult_bone_implanted_into_nonobese_diabetic/severe_combined_immunodeficient_mice_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=12727825 DB - PRIME DP - Unbound Medicine ER -