Morphological and immunohistochemical characteristics of a cell line originated from noninvasive human bladder transitional-cell carcinoma.

Abstract

A cell line (IG) was derived from a noninvasive transitional cell carcinoma grade II. The cells were propagated in vitro for 9 months, had a low proliferative capacity, formed tumor nodules, and showed four characteristic morphological stages. Primary epithelial-like cells were characterized as stage I; fibroblast-like cells with loss of contact inhibition of growth as stage II; fibroblast-like cells with long cytoplasmic projections, massive glycosaminoglycan content and tumor nodule formation as stage III; and, as stage IV, granulated stellate cells. The cell culture progressed cytologically from well-differentiated stage I to less-differentiated stage IV. The four stages were confirmed and examined by electron microscopy. Immunoreactivity for fibronectin, keratin, epithelial membrane antigen and carcinoembryonic antigen shown by the cell line and the tissue indicates that the cell line represents the original cell population in the tumor. Glycosaminoglycan production by these cells was found to be responsible for the formation of tumor nodules which appeared in culture at the same time as the patient had developed an invasive bladder tumor. Glycosaminoglycans were observed as a massive accumulation intracellularly and extracellularly, as rods or thick slices in layers of adherent vesicles and granules covering the cell culture. Normal bladder epithelial cells and fibroblasts grew in monolayer, showed contact inhibition of growth, were devoid of intracellularly accumulated glycosaminoglycans and produced uniform extracellular matrix different from that of IG cells.