High tumorigenicity of human acute monocytic leukemic cell Line SHI-1 in nude mice and its mechanism / 中国实验血液学杂志

ABSTRACT

This study was purposed to explore the tumorigenicity of a novel human monocytic leukemic cell line SHI-1 in nude mice and its mechinism. The tumorigenicity in mice was evaluated in sixteen nude mice subcutaneously injected with the SHI-1 cell line. The tumor specimen was studied by the conventional pathologic examination. The mononuclear cells (MNC) of the tumor was assayed by RHG banding, the transcription of MLL-AF6 fusion gene and the VEGF gene was detected by RT-PCR. Gelatin zymography method was used to study the expression of MMP-9 and MMP-2 in the supernatant of the SHI-1 cell line. Matrigel invasion assay was employed for the study of migration of the SHI-1 cell in vitro. The results showed that the tumor masses were found in all sixteen mude mice after subcutaneous injection of SHI-1 cells, the tumor mass was mainly composed of leukemia cells, the transcription of MLL-AF6 fusion gene and VEGF gene was proved by RT-PCR analysis, the expressions of MMP-2 and MMP-9 in the serum-free culture supernatant of the SHI-1 cell line were significantly higher than those in U937, K562, and NB4 cell lines. The SHI-1 cell line exhibited significantly higher in vitro invasiveness than other leukemia cell lines, the blocking antibody of MMP-2 could inhibit the migration of the SHI-1 cell line significantly. It is concluded that the SHI-1 cell line presents higher tumorigenicity in nude mice than other leukemia cell line and the mechanism is associated with p53 gene alteration, high transcription level of VEGF gene, high expression level of MMP, and significantly higher invasiveness.