Heterogeneity and susceptibility to apoptosis of human renal carcinoma cells in vitro

Tumors are heterogeneous in terms of morphology and susceptibility to drugs or radiation. Among primary and metastatic cells of a human renal carcinoma, a population (type II) of larger cells with prominent nucleoli, eosinophilic globules of intermediate filaments in paranuclear bundles, margination of subcellular organelles and peripheral pools of glycogen was evident. Paranuclear structures were recognized by monoclonal antibodies specific for cytokeratin 8, 18 and 19, but not by vimentin specific antibodies. We propagated a cell line in vitro (referred to as BKR cells), and observed culture in vitro, the almost complete disappearance of the type II cells. Pharmacological agents that influence cell differentiation, such as retinoic acid, rescued the expression of type II cells in vitro. Long-term treatments with insulin or α-interferon, but not with the epithelial growth factor (EGF), similarly differentiated BKR cells and abated their susceptibility to spontaneous and actinomycin-D induced apoptosis. These data support the contention that differentiation of tumor cells is actively maintained in vivo and further strengthen the caveat on tumor lines stabilized in vitro, that poorly represent the morphologic and antigenic heterogeneity of neoplasms in vivo.