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1 May 2012
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Metastasis to bone is the most frequent cause of breast cancer morbidity and mortality. Osteolytic lesions are formed as a result of cancer-induced increased osteoclast activity. Heparin and heparin-like glycosaminoglycans (HLGAGs), which are commonly used to prevent venous thromboembolism, have previously been shown to prolong survival of cancer patients. The effects of HLGAGs on human osteoclasts were studied in vitro by culturing human osteoclasts on bovine bone slices in the presence of different concentrations of HLGAGs for three days. Multinuclear TRACP-positive osteoclasts were visualized by staining the nuclei with Hoechst and the tartrate-resistant acid phosphatase (TRACP) content of the cells using a leukocyte acid phosphatase kit. Resorption pits were visualized using TRITC-conjugated WGA lectin. The upper images of resorption pits (X 20 magnification) indicate that a high-molecular-weight E. coli K5-derived heparin-like polysaccharide (K5-NSOS) inhibits bone resorption activity of osteoclasts (examples of resorption pits are outlined in blue). K5-NSOS did not affect the amount of TRACP positive osteoclasts, as indicated by the lower images (X 10 magnification). Because K5-NSOS is an antimetastatic and antiresorptive compound with low anticoagulant activity, it is a potential therapeutic agent to prevent and/or treat breast cancer metastases. For further details, please see Pollari and colleagues on page 597 in this issue. - PDF Icon PDF LinkTable of Contents
ISSN 1541-7786
EISSN 1557-3125
Molecular Cancer Research
Table of Contents
Highlights
Review
Angiogenesis, Metastasis, and the Cellular Microenvironment
Heparin-like Polysaccharides Reduce Osteolytic Bone Destruction and Tumor Growth in a Mouse Model of Breast Cancer Bone Metastasis
Sirkku Pollari; Rami S. Käkönen; Khalid S. Mohammad; Jukka P. Rissanen; Jussi M. Halleen; Anni Wärri; Liisa Nissinen; Marjo Pihlavisto; Anne Marjamäki; Merja Perälä; Theresa A. Guise; Olli Kallioniemi; Sanna-Maria Käkönen
Cell Cycle, Cell Death, and Senescence
DNA Damage and Cellular Stress Responses
Signaling and Regulation
Journal Archive
Molecular Cancer Research
(2002-Present; volumes 1-current)Published monthly since November, 2002.
(ISSN 0008-5472)
Cell Growth & Differentiation
(1990-2002; volumes 1-13)Published monthly 1990- September, 2002.
(ISSN 1044-9523)
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