Renal cell carcinoma in the Wistar-Lewis rat: a model for studying the mechanisms of cholesterol acquisition by a tumor in vivo.
Renal adenocarcinoma implanted into isogeneic Wistar-Lewis rats closely resembles human renal cancer. This paper characterizes the tumor's growth rate, metastatic potential, and its light and electron microscopic appearance. Additionally, for the first time, the pathways through which a tumor acquires the cholesterol needed for growth were quantified in vivo. Two 1-mg pieces of renal carcinoma were implanted beneath the renal capsule of 80 Wistar-Lewis rats. Of the implanted tumors 95% "took" and grew rapidly, doubling every 2.6 days initially. Growth slowed, however, to a doubling time of 8.3 days by the fifth wk. Twenty rats underwent surgical resection of the primary tumor 5 wk after implantation. Of these, 85% subsequently developed lung metastases. Histologically, the tumor had a clear-cell appearance due to the presence of large vacuoles, some of which contained glycogen. The esterified cholesterol content of the tumor was 3-fold higher than normal kidney during the initial period of rapid tumor growth and increased to a 14-fold elevation by 12 wk. The normal kidney in vivo had a high rate of uptake of cholesterol carried in low density lipoproteins and a low rate of de novo sterol synthesis. In contrast, the renal carcinoma lost most of its low density lipoprotein uptake activity and, instead, acquired the cholesterol needed for growth by a 5-fold increase in the rate of de novo cholesterol synthesis. This model may prove valuable in both testing therapeutic strategies directed against human renal cancer and understanding the regulation of cholesterol homeostasis in a growing cancer.
D000818:Animals; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D002784:Cholesterol / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000378:metabolism; D004195:Disease Models, Animal; D007668:Kidney / Q000378:metabolism; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D011973:Receptors, LDL / Q000378:metabolism
D008078:Cholesterol, LDL; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D002784:Cholesterol