Anti-PTK2 monoclonal antibody, clone 20I8B7

Although osteosarcoma is the most common bone malignancy, the molecular and cellular mechanisms influencing its pathogenesis have remained elusive. Prion proteins (PRNP and PRND), known mostly for its involvement in neurodegenerative spongiform encephalopathies, have been recently demonstrated to be involved in resistance to apoptosis, tumorigenesis, proliferation, and metastasis. The main aim of research was to study whether prion proteins were over-expressed in human osteosarcoma, and if prion proteins could have a role also in osteosarcomas. We evaluated differential gene expression between 22 cases of osteosarcoma and 40 cases of normal bone specimens through cDNA microarray analysis spanning a substantial fraction of the human genome. PRNP and PRND are significantly over-expressed in osteosarcoma. PRNP and PRND appear involved with some important genes related to tumorigenesis and apoptosis. PRNP is linked to PTK2, RBBP9, and TGFB1 while PRND is linked to TNFSF10, BCL2A1, NFKB2, and TP53RK. Increased expression on Affymetrix arrays of prion proteins seems to be associated with the development of osteosarcoma. Prions seem to induce a negative regulation of apoptosis, thus promoting osteosarcoma development and progression. Osteosarcoma is a very aggressive tumor and even after modern chemotherapy and excision of tumors efforts are needed to improve clinical outcome. Since Prion proteins seem to be related to osteosarcoma development, their inhibition could represent a new approach to the molecular treatment of osteosarcoma. (c) 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:10041012, 2012

The NG2 chondroitin sulfate proteoglycan is a membrane-spanning molecule expressed by immature precursor cells in a variety of developing tissues. In tightly adherent cell liner; with a flattened morphology, NG2 is organized on the cell surface in linear arrays that are highly co-localized with actin and myosin-containing stress fibers in the cytoskeleton. In contrast, microtubules and intermediate filaments in the cytoskeleton exhibit completely different patterns of organization, suggesting that NG2 may use microfilamentous stress fibers as a means of cytoskeletal anchorage. Consistent with this is the observation that cytochalasin D disrupts the organization of both stress fibers in the cytoskeleton and NG2 on the cell surface. Very similar linear cell surface arrays are also seen with three other cell surface molecules thought to interact with the actin cytoskeleton: the alpha(5) beta(1) integrin, the CD44 proteoglycan, and the Li neuronal cell adhesion molecule. Since the cytoplasmic domains of these four molecules are dissimilar, it seems possible that cytoskeletal anchorage in each case may occur via different mechanisms. One indication of such differences can be seen in colchicine-treated cells which have lost their flattened morphology but still retain long actin-positive tendrils as remnants of the actin cytoskeleton. NG2 and alpha(5) beta(1) are associated with these tendrils while CD44 and L1 are not, suggesting that at least two subclasses of cell surface molecules exist which can interact with different subdomains of the actin cytoskeleton. (C) 1996 Wiley-Liss, Inc.