[Role of organ specific fibroblasts in metastasis of human renal cell carcinoma: regulation of type IV collagenase production from human renal cell carcinoma by organ specific fibroblasts].
An orthotopic metastatic human renal cell carcinoma model in nude mice was established to evaluate the mechanism of metastasis as a preliminary phase in the development of a treatment to prevent cancer metastasis. The effect of host fibroblasts from different organs on the production of type IV collagenase by human renal cell carcinoma and the factors which influenced the enzyme production and secretion by fibroblasts were also investigated. KG-2 cells were established from human renal cell carcinoma, and produced tumors following implantation to both the subrenal capsular space (orthotopic site) and subcutis (ectopic site). Histologically, the tumors in the subcuit (SC tumors) were well encapsulated with a thick fibrous capsule and did not produce metastasis or invasion, whereas those in the subrenal capsular space (SRC tumors) lacked a fibrous capsule and produced metastasis at the lung or regional lymph nodes. The production of type IV collagenase in conditioned media from metastatic SRC tumors and lung metastatic lesions was larger than that from non-metastatic SC tumors. The conditioned media separated from mouse kidney or lung fibroblasts stimulated the production of type IV collagenase by KG-2 cells, whereas, that separated from mouse skin fibroblasts decreased the enzyme production. The production of type IV collagenase by KG-2 cells was stimulated by cocultured KG-2 cells and fibroblasts from the kidney or lung, whereas it was suppressed by cocultured KG-2 cells and skin fibroblasts.(ABSTRACT TRUNCATED AT 250 WORDS)
Gohji
K
K
Department of Urology, Kobe University School of Medicine.
Kamidono
S
S
D000818:Animals; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000556:secondary*; D017364:Collagenases / Q000096:biosynthesis*; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology*; D020780:Matrix Metalloproteinase 9; D051379:Mice; D008819:Mice, Nude; D013370:Subrenal Capsule Assay; D016212:Transforming Growth Factor beta / Q000502:physiology
D016212:Transforming Growth Factor beta; D017364:Collagenases; D020780:Matrix Metalloproteinase 9