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Renal cell carcinoma in tissue culture secretes nondialyzable product that stimulates bone resorption in organ‐cultured mouse calvaria
Author(s) -
Lerner Ulf H.,
Ljungberg Börje
Publication year - 1989
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650040311
Subject(s) - calvaria , bone resorption , resorption , bone cell , chemistry , endocrinology , in vivo , medicine , organ culture , hydroxyproline , prostaglandin e2 , kidney , in vitro , biology , biochemistry , microbiology and biotechnology
The bone‐resorbing capacity of human renal cell carcinomas in vitro has been examined. Bone resorption in cultures of mouse calvarial bones was assessed by the release of 45 Ca from bones prelabeled in vivo and the mobilization of stable calcium and inorganic phosphate from nonlabeled bones. In addition, bone organic matrix degradation was determined either by the release of 3 H from [ 3 H]proline‐labeled bones or by the loss of hydroxyproline from bone explants during culture. Tumor tissue‐conditioned media (TCM) from 13 of 13 renal cell carcinomas stimulated bone resorption in a dose‐dependent manner. From 5 of 13 kidneys with renal cell carcinoma, normal kidney cortex tissue was cultured and 4 of these 5 also produced bone‐resorbing activity, but the amount was much less compared with the tumor tissue. The stimulatory effect of TCM on 45 Ca release could be observed first after 12–24 h of culture. The effect could be inhibited by calcitonin but not by inhibitors of prostaglandin synthesis. The production of bone‐resorbing activity by tumor cells could be inhibited by indomethacin and meclofenamic acid. In some tumors, the inhibition by indomethacin was total, whereas in other tumors only partial inhibition could be obtained. In 3 of 4, TCM bone‐resorbing activity could be found in the retentate after dialysis. The results show that fresh human renal cell carcinoma tissue can elaborate prostanoid as well as nonprostanoid products that can stimulate bone resorption.