Production of parathyroid hormone‐related protein in two new cell lines of renal cell carcinoma

Abstract

Background: Hypercalcemia is the most common of all paraneoplastic syndromes and has been reported to appear in up to 20% of patients with renal cell carcinoma (RCC). Humoral hypercalcemia of malignancy is believed to be induced when parathyroid hormone‐related protein (PTHrP) is excessively produced in cancer cells and impairs the homeostasis of serum calcium concentrations. Methods: Cancer cells were isolated from a surgical specimen and successfully cultured in a monolayer. The present study describes the establishment and characterization of new cell lines of RCC. Results: Two different cell lines, designated SMRC‐1 and SMRC‐3, were established from human RCC, each of which had been continuously secreting PTHrP in vitro. The patient from whom the SMRC‐3 cells were obtained was shown to have elevated levels of PTHrP and resultant hypercalcemia. Cultured SMRC‐1 was spindle‐shaped in morphology. SMRC‐3 had pleomorphic polygonal shapes and formed typical epithelial monolayers. Both cell types secreted intact, C‐terminal PTHrP and interleukin‐6 in the culture medium. Cellular messenger RNA of PTHrP was analyzed by reverse transcriptase–polymerase chain reaction. The SMRC‐1 cells showed chromosome numbers ranging from 42 to 47 with consistent structural abnormalities of add(4)(q23~25) and add(6)(q13). The chromosomal analysis of SMRC‐3 revealed a modal number of 95 with consistent structural abnormalities of add(1)(p36) and der(1;3)(q10;p10). Conclusions: These cell lines could be good models for investigating the mechanism of PTHrP production and the relationship between this hormone and hypercalcemia.