Hypercalcemia and cosecretion of interleukin-6 and parathyroid hormone related peptide by a human renal cell carcinoma implanted into nude mice.
Humoral hypercalcemia of malignancy is a paraneoplastic syndrome believed to be due to production by the tumor of substances that stimulate osteoclastic bone resorption primarily. The human renal cell carcinoma cell line RC-8, grown in nude mice, was investigated for factors involved in renal cancer-induced hypercalcemia. At a tumor load of 200 to 400 mm.3 the mice developed hypercalcemia and hypophosphatemia associated with a rise in serum 1,25-dihydroxyvitamin D concentration and cachexia. The tumor released 1) significant amounts of human interleukin-6 (IL-6) and 2) parathyroid hormone-related peptide (PTHrP) into the circulation. Cancer cells further expressed mRNA for both human IL-6 and PTHrP. No secretion of human tumor necrosis factor-alpha or interleukin-1 beta could be demonstrated in the circulation of the host. Antibodies to IL-6 caused a significant (p = 0.043) inhibition of tumor growth and decreased serum calcium concentrations compared with control animals. Our data suggest that IL-6 is involved, either directly or indirectly, in the development of hypercalcemia in renal cell carcinoma.
Weissglas
M
M
Department of Urology, University Hospital of Leiden, The Netherlands.
Schamhart
D
D
Löwik
C
C
Papapoulos
S
S
Vos
P
P
Kurth
K H
KH
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000150:complications / Q000378:metabolism*; D006801:Humans; D006934:Hypercalcemia / Q000209:etiology*; D015850:Interleukin-6 / Q000378:metabolism*; D007680:Kidney Neoplasms / Q000150:complications / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000378:metabolism*; D009368:Neoplasm Transplantation; D044162:Parathyroid Hormone-Related Protein; D011188:Potassium / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*
D015850:Interleukin-6; D009363:Neoplasm Proteins; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D011188:Potassium; D002118:Calcium