Monoclonal antibodies to osteoclastomas (giant cell bone tumors): definition of osteoclast-specific cellular antigens

Abstract

The cellular origin of the osteoclast, the major agent of bone resorption, remains controversial despite the demonstration that osteoclasts form by fusion of mononuclear cells that are ultimately derived from a bone marrow stem cell. One view is that they are the terminally differentiated progeny of mononuclear phagocytic cells. However, we have previously provided evidence, from functional and phenotypic studies of rodent and human osteoclasts, that raises the possibility that osteoclasts form a separate cell lineage from conventional hemopoietic cells and macrophages in particular. In an attempt to elucidate this question, we have used monoclonal antibody techniques to examine the relationship between osteoclasts and other bone marrow-derived cells. By using osteoclasts from osteoclastomas (giant cell tumors of bone) for immunizations, we have produced 11 mouse hybridomas secreting monoclonal antibodies reacting with osteoclasts in normal human fetal bone and a variety of neoplastic and non-neoplastic bone lesions. Eight antibodies in 4 reactivity sets have been shown to recognize membrane antigens, whereas a further 3 react with cytoplasmic determinants. In 7 there is no cross-reactivity with macrophages in a wide range of tissues, thus effectively differentiating between these two cell types. These antibodies will prove useful for the identification of osteoclasts in tissues and in the separation of their circulating precursors, thus allowing an experimental approach to be made to many of the outstanding questions regarding the developmental pathobiology of the osteoclast.