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Role of Interleukin‐6 in Uncoupling of Bone In Vivo in a Human Squamous Carcinoma Coproducing Parathyroid Hormone‐Related Peptide and Interleukin‐6
Author(s) -
Nagai Yumiko,
Yamato Hideyuki,
Akaogi Keiko,
Hirose Kunitaka,
Ueyama Yoshito,
Ikeda Kyoji,
Matsumoto Toshio,
Fujita Toshiro,
Ogata Etsuro
Publication year - 1998
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.1998.13.4.664
Subject(s) - bone resorption , endocrinology , medicine , osteoclast , parathyroid hormone , osteopontin , in vivo , interleukin , osteoblast , chemistry , cytokine , biology , cancer research , receptor , in vitro , calcium , microbiology and biotechnology , biochemistry
OCC tumor has been established from a human squamous carcinoma associated with humoral hypercalcemia of malignancy (HHM) and shown to overproduce parathyroid hormone‐related peptide (PTHrP) and cause aggressive hypercalcemia when implanted into nude rats. In the present study, we have demonstrated by reverse transcription‐polymerase chain reaction and Northern blot analysis that OCC tumor also overexpressed interleukin 6 (IL‐6) mRNA and that tumor‐bearing animals exhibited a marked increase in plasma IL‐6 as well as PTHrP concentrations. When a monoclonal antibody against human IL‐6 was injected to block the activities of tumor‐derived IL‐6, bone loss in tumor‐bearing animals was significantly prevented. Quantitative bone histomorphometric analysis revealed that treatment with anti–IL‐6 antibody caused a substantial decrease in both osteoclast number and eroded surface (as parameters of bone resorption) and also a significant increase in the mineral apposition rate, but little effect on the osteoblastic surface. These results provide in vivo evidence suggesting that in tumors coproducing IL‐6 and PTHrP, IL‐6 is involved not only in the acceleration of osteoclastic bone resorption but also, at least in part, in the suppression of osteoblastic functions in HHM syndrome.