Factor derived from human lung carcinoma associated with hypercalcemia mimics the effects of parathyroid hormone on phosphate transport in cultured renal epithelia.
A decrease in renal tubular reabsorption of inorganic phosphate (Pi) can be observed in hypercalcemia of malignancy. In the present study we investigated the effect of serum-free conditioned medium (CM) from cells, derived from a lung carcinoma (BEN) of a hypercalcemic patient, and of PTH on cyclic AMP (cAMP) production and sodium-dependent Pi transport (NaPiT) in epithelia of two renal cell lines. In opossum kidney cells (OK), PTH is known to enhance cAMP production and inhibit NaPiT; in contrast, in LLC-PK1 cells, PTH has no effect on NaPiT since this kidney cell line is devoid of PTH receptors. In OK cells, BEN CM induced a three- to fourfold increase of cAMP production, which was blunted by the PTH inhibitors bPTH(3-34) and bPTH(7-34). NaPiT, as assessed by measuring the initial rate of Pi uptake, was inhibited in a dose-dependent manner by BEN CM, with an effect maximal between 1h30 and 6 hr of incubation (40 +/- 4% and 47 +/- 4%, respectively), corresponding to the effect produced by 1-3 nM bPTH(1-34). The Na-dependent transport of a glucose analog was affected neither by BEN CM nor by PTH. In LLC-PK1 cells, neither BEN CM nor PTH altered cAMP production nor NaPiT after 1h30 of incubation. At 6 hr, BEN CM caused a slight decrease in NaPiT. In conclusion, these results constitute the first evidence of a direct and selective inhibition by tumor-derived factor(s) of NaPiT in cultured renal epithelia. Most of the renal NaPiT inhibitory activity produced by the lung tumor required the presence of a PTH receptor-adenylate cyclase system.(ABSTRACT TRUNCATED AT 250 WORDS)
Pizurki
L
L
Department of Medicine, University Hospital, Geneva, Switzerland.
Rizzoli
R
R
Caverzasio
J
J
Mundy
G
G
Bonjour
J P
JP
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000503:physiopathology*; D002460:Cell Line; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006934:Hypercalcemia / Q000503:physiopathology*; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D008175:Lung Neoplasms / Q000503:physiopathology*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010710:Phosphates / Q000378:metabolism*; D019379:Teriparatide
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D010710:Phosphates; C058350:parathyroid hormone (7-34); D019379:Teriparatide