Up-regulation of type XIX collagen in rhabdomyosarcoma cells accompanies myogenic differentiation

Rhabdomyosarcomas are known to recapitulate some of the early events in ske letal muscle embryogenesis, and cultures derived from these tumors have bee n extensively used to elucidate processes associated with the differentiati on of primitive mesenchymal cells. These neoplasms have also provided impor tant systems for studying different collagen types. This aspect is particul arly relevant to type XIX collagen, which was originally identified from rh abdomyosarcoma cDNA clones. Although this collagen has been localized in vi vo to basement membrane zones in a wide variety of tissues, including skele tal muscle, the tumor cells appear to be a unique source of its expression in vitro. We have found that one particular cell line-derived from a perite sticular embryonal rhabdomyosarcoma-produced relatively large amounts of ty pe XIX collagen, especially in those rare instances in which these cells ap pear to spontaneously differentiate. To characterize this phenomenon, tumor cells were grown under conditions known to induce differentiation in norma l myoblast cultures. In response to this treatment, the typical tumor cell morphology consistently and reproducibly switched from polygonal to round/s pindle-shaped with the subsequent appearance of some structures resembling myotubes. Concurrently, the cultures commenced a dramatic up-regulation of type XIX collagen and skeletal muscle myosin heavy chain and alpha-actinin in a time-dependent fashion, whereas protein and mRNA levels of other matri x proteins were either decreased or unchanged. Moreover, immunocytochemical analysis revealed that only a subpopulation of the cells was responsible f or the increased synthesis of type XIX collagen, alpha-actinin, and myosin, and that the same cells which stained positive for the collagen also stain ed positive for the muscle proteins. Taken together, the results suggested that type XIX collagen may be involved in the initial stages of skeletal mu scle cell differentiation. (C) 1999 Academic Press.