title: 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.
authors.affiliation: Department of Urology, Kidney Disease Center, Division of Morphological Science, Biomedical Research Center, Saitama Medical School, Saitama, Japan. camtmune@saitama-med.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Ueno
authors.forename: M
authors.initials: M
authors.lastname: Akita
authors.forename: S I
authors.initials: SI
authors.lastname: Ban
authors.forename: T
authors.initials: T
authors.lastname: Ohigashi
authors.forename: S
authors.initials: S
authors.lastname: Yanagita
authors.forename: M
authors.initials: M
authors.lastname: Iida
authors.forename: N
authors.initials: N
authors.lastname: Deguchi
mesh_terms: D000328:Adult; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division; D002869:Chromosome Aberrations; D002878:Chromosomes, Human, Pair 1; D006801:Humans; D006934:Hypercalcemia / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007621:Karyotyping; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D044162:Parathyroid Hormone-Related Protein; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000378:metabolism*
chemical_list: D015850:Interleukin-6; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D012333:RNA, Messenger