Role of interleukin-6 in uncoupling of bone in vivo in a human squamous carcinoma coproducing parathyroid hormone-related peptide and interleukin-6

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
Y NagaiE Ogata

Abstract

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 o...Continue Reading

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Citations

Feb 8, 2000·Clinica Chimica Acta; International Journal of Clinical Chemistry·J L MotellónP Esbrit
May 15, 2002·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Yasuhiro TakeuchiToshiro Fujita
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Nov 14, 2000·Clinica Chimica Acta; International Journal of Clinical Chemistry·J L MotellónP Esbrit
Apr 15, 1999·Journal of the American Society of Nephrology : JASN·F De MiguelP Esbrit

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