Renal cell carcinoma and natural killer cells: studies in a novel rat model in vitro and in vivo.
The transplantable rat kidney carcinoma (RKC) provides an excellent experimental model for immunological and therapeutic studies of renal cell carcinoma. In this report, we define the biological characteristics of RKC and explore the interactions between RKC and natural killer (NK) cells. RKC, a transplantable tumor of spontaneous origin, grows progressively over a 12-week period and metastasizes to the lung when implanted orthotopically in the kidneys of female Lewis rats. Rats bearing RKC survived for an average of 10.5 +/- 1.5 (SD) weeks postimplantation. Lung metastases were visible between 7.5 and 8.5 weeks postimplantation, and by 9 to 10 weeks the incidence of metastases reached approximately 67%. Injection of the NK cell-specific monoclonal antibody 3.2.3 depleted Lewis rats of their NK activity for up to 14 days. Adherent lymphokine-activated killer cells generated from the spleens of 3.2.3-injected rats were significantly less lytic than those from control rats and contained a significantly lower percentage of 3.2.3+ cells when analyzed by flow cytometry. Groups of rats were implanted with RKC and received injections of 3.2.3 biweekly to maintain depletion of NK cells or of a control antibody, NK1.1, specific for mouse NK cells. At 10 weeks postimplantation, 3.2.3-injected rats had significantly (P < or = 0.005) larger tumors (104.4 +/- 20.1 g) than NK1.1-injected rats (75.4 +/- 13.9 g). Spleen cells and peripheral blood cells from uninjected, tumor-bearing rats had a slight but nonsignificant decrease in NK activity against 51Cr-labeled YAC-1 targets over the course of RKC progression. The activity of adherent lymphokine-activated killer cells from tumor-bearing rats was lower than that from normal rats, but not significantly. Cultured RKC cells were killed by both splenic NK cells and adherent lymphokine-activated killer cells. These data demonstrate that RKC is NK sensitive and that tumor growth does not abrogate NK activity. The RKC tumor provides a model system for the analysis of immunological factors in renal cell carcinoma growth and presents opportunities for testing therapeutic interventions in a system that closely mimics the human disease.
Winter
B K
BK
Center for Bioengineering, University of Washington, Seattle 98195.
Wu
S
S
Nelson
A C
AC
Pollack
S B
SB
D000818:Animals; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000473:pathology* / Q000556:secondary; D002448:Cell Adhesion / Q000502:physiology; D016923:Cell Death / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D007680:Kidney Neoplasms / Q000276:immunology / Q000473:pathology*; D015979:Killer Cells, Lymphokine-Activated / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology / Q000502:physiology*; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D051381:Rats; D011917:Rats, Inbred Lew