BACKGROUND: Parathyroid hormone-related protein (PTHrP) has been implicated in bone metastasis. However, the effects on bone metastasis of blocking the PTHrP function have not been tested in the clinic. Here, the effects of a humanized anti-PTHrP monoclonal antibody (mAb) on bone metastasis in a human xenograft model are shown. MATERIALS AND METHODS: Subline MDA-5a, with high bone metastatic activity, was established from the human breast cancer cell line MDA-MB-231. Mice were injected with MDA-5a and an anti-PTHrP monoclonal antibody (mAb) raised against human PTHrP (1-34); bone metastasis was evaluated by X-ray photography. RESULTS: MDA-5a produced elevated levels of PTHrP, Interleukin 8 (IL-8), IL-6 and matrix metalloproteinase 1 (MMP-1) and frequently metastasized to the bone. Administration of the humanized anti-PTHrP mAb significantly suppressed osteolytic bone metastasis of MDA-5a and caused osteogenesis at the sites of metastasis. CONCLUSION: The humanized anti-PTHrP mAb was effective against bone metastasis by inducing osteogenesis and, therefore, will provide a new treatment option for bone metastasis in breast cancer.
BACKGROUND:Parathyroid hormone-related protein (PTHrP) has been implicated in bone metastasis. However, the effects on bone metastasis of blocking the PTHrP function have not been tested in the clinic. Here, the effects of a humanized anti-PTHrP monoclonal antibody (mAb) on bone metastasis in a human xenograft model are shown. MATERIALS AND METHODS: Subline MDA-5a, with high bone metastatic activity, was established from the humanbreast cancer cell line MDA-MB-231. Mice were injected with MDA-5a and an anti-PTHrP monoclonal antibody (mAb) raised against humanPTHrP (1-34); bone metastasis was evaluated by X-ray photography. RESULTS: MDA-5a produced elevated levels of PTHrP, Interleukin 8 (IL-8), IL-6 and matrix metalloproteinase 1 (MMP-1) and frequently metastasized to the bone. Administration of the humanized anti-PTHrP mAb significantly suppressed osteolytic bone metastasis of MDA-5a and caused osteogenesis at the sites of metastasis. CONCLUSION: The humanized anti-PTHrP mAb was effective against bone metastasis by inducing osteogenesis and, therefore, will provide a new treatment option for bone metastasis in breast cancer.
Authors: Rachelle W Johnson; Mai P Nguyen; Susan S Padalecki; Barry G Grubbs; Alyssa R Merkel; Babatunde O Oyajobi; Lynn M Matrisian; Gregory R Mundy; Julie A Sterling Journal: Cancer Res Date: 2010-12-28 Impact factor: 12.701
Authors: Jiarong Li; Andrew C Karaplis; Dao C Huang; Peter M Siegel; Anne Camirand; Xian Fang Yang; William J Muller; Richard Kremer Journal: J Clin Invest Date: 2011-11-07 Impact factor: 14.808
Authors: William J McKinstry; Galina Polekhina; Hannelore Diefenbach-Jagger; Patricia W M Ho; Koh Sato; Etsuro Onuma; Matthew T Gillespie; T John Martin; Michael W Parker Journal: J Biol Chem Date: 2009-04-04 Impact factor: 5.157
Authors: Joseph Vanderburgh; Jordan L Hill; Mukesh K Gupta; Kristin A Kwakwa; Sean K Wang; Kathleen Moyer; Sean K Bedingfield; Alyssa R Merkel; Richard d'Arcy; Scott A Guelcher; Julie A Rhoades; Craig L Duvall Journal: ACS Nano Date: 2020-01-08 Impact factor: 15.881