Regulation of parathyroid hormone-related protein production in a human lung squamous cell carcinoma line.
The synthesis and release of parathyroid hormone-related protein (PTHrP) could be influenced in a paracrine or autocrine manner by substances present around or inside tumours, such as bone or stromal cell-derived cytokines, factors produced by the tumour itself or by peritumoural inflammatory cells. We investigated the effects of various cytokines known to be synthesized by osteoblasts, stromal cells, leucocytes or cancer cells, on PTHrP production by the human lung squamous cell carcinoma line BEN. The influence of tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) was studied, and compared with those of insulin-like growth factors-I and -II (IGF-I, IGF-II), or macrophage- or granulocyte-macrophage colony-stimulating factors (M-CSF, GM-CSF). TNF-alpha caused a 1.9 +/- 0.1-fold increase in immunoreactive PTHrP production, which was maximal by 24 h of incubation. IL-6 caused a 2.3 +/- 0.2-fold increase, which was maximal by 16 h. These effects, which were time- and concentration-dependent, were blocked by monoclonal antibodies raised against the corresponding cytokine. An increase of PTHrP mRNA was found in IL-6-treated cells. IGF-I and IGF-II increased PTHrP production by 2.0 +/- 0.3- and 2.3 +/- 0.1-fold respectively. Neither M-CSF nor GM-CSF altered PTHrP production up to 64 h of incubation. PTHrP production was not affected by varying extracellular calcium concentrations, but was decreased by incubation with 100 nmol/l dexamethasone.(ABSTRACT TRUNCATED AT 250 WORDS)
Rizzoli
R
R
Department of Medicine, University Hospital, Geneva, Switzerland.
Feyen
J H
JH
Grau
G
G
Wohlwend
A
A
Sappino
A P
AP
Bonjour
J P
JP
D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008175:Lung Neoplasms / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D010281:Parathyroid Hormone / Q000096:biosynthesis*; D044162:Parathyroid Hormone-Related Protein; D014176:Protein Biosynthesis; D013268:Stimulation, Chemical; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D015850:Interleukin-6; D009363:Neoplasm Proteins; C470121:PTHLH protein, human; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D014409:Tumor Necrosis Factor-alpha; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D003907:Dexamethasone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor