Analysis of a mouse monoclonal antibody that reacts with a specific region of the human proximal tubule and subsets renal cell carcinomas
Carcinoma, Renal Cell
Kidney Tubules, Proximal
Murine monoclonal antibody (mAb) F31 detects a heat-stable antigen (URO-8) found in the acidic lipid fraction of renal cancer cell extracts. Serological analysis of mAb F31 reactivity was assayed on 176 human cell lines. mAb F31 reacted with 38 of 45 renal cancers, a subpopulation of cells in primary cultures of normal renal epithelia, and two of 13 colon, two of 15 lung, and four of five ovarian cancers. No other epithelial, hematopoietic, or neuroectodermal cell lines tested were reactive. Immunofluorescence and immunoperoxidase analyses of fresh frozen tissue sections revealed mAb F31 reactivity in kidney, gastrointestinal tract, biliary canaliculi, bronchial epithelium, and skin. Within the kidney, mAb F31 immunoreactivity was confined to the straight portion of the proximal tubule. A panel composed of previously characterized mAbs as well as mAb F31 defines the antigenic phenotype of proximal convoluted tubular cells as URO-2+/URO-3+/URO-4+/URO-10+/URO-8-/URO-5-; proximal straight tubular cells as URO-2+/URO-3+/URO-4+/URO-10-/URO-8+/URO-5-; and cells of the descending thin limb of Henle as URO-2-/URO-3+ or -/URO-4+/URO-10-/URO-8-/URO-5+. While adult proximal tubular cells demonstrated reciprocal expression of URO-8 and URO-10, fetal kidney proximal tubule progenitor cells coexpressed both antigens (URO-10+/URO-8+). Fifty renal cancer specimens were typed with these antibodies. Fourteen cases were URO-10+/URO-8-, ten cases were URO-10-/URO-8+, and 25 cases expressed both antigens (URO-10+/URO-8+). These phenotypes are consistent with derivation of these particular subsets from the proximal convoluted tubule, the pars recta, or a proximal tubule progenitor cell, respectively. Only one specimen failed to express either URO-8 or URO-10.