Expression of the metalloproteinase matrilysin in DU-145 cells increases their invasive potential in severe combined immunodeficient mice.
Expression of the metalloproteinase matrilysin in DU-145 cells increases their invasive potential in severe combined immunodeficient mice.
复制标题
DOI：
--
复制
发表时间：
1993-01
期刊：
影响因子：
11.2
通讯作者：
W. Powell;J. Knox;M. Navre;T. Grogan;J. Kittelson;Raymond B. Nagle;G. Bowden
中科院分区：
文献类型：
--
作者：
W. Powell;J. Knox;M. Navre;T. Grogan;J. Kittelson;Raymond B. Nagle;G. Bowden
人类前列腺癌在其扩散速度上表现出高度的可变性，这可能主要是由于肿瘤细胞侵袭潜力的差异。基底膜和间质细胞外基质的降解部分是由基质金属蛋白酶（MMPs）的分泌介导的。基质溶素（PUMP-1, MMP-7）和明胶酶A （M(r) 72000 IV型胶原酶，MMP-2）在前列腺癌中过度表达。我们在致瘤性但非转移性的人前列腺肿瘤细胞系DU-145中表达了单一MMP基质溶素，以确定基质溶素是否在前列腺肿瘤细胞侵袭中具有功能作用。通过严重联合免疫缺陷小鼠肿瘤细胞侵袭模型检测，表达基质溶素的DU-145细胞比仅转染载体的细胞系侵袭性更强。单纯载体转染的DU-145细胞在9只小鼠中只有1只（11%）侵入膈膜，而母体溶素转染的DU-145细胞在18只小鼠中有12只（66%）侵入膈膜。对照组与基质溶素转染细胞间差异有统计学意义（P < 0.006）。这些结果表明基质溶素在前列腺癌通过上皮基底膜和周围基质的初始侵袭过程中发挥了功能作用。
Human prostate cancer displays a high degree of variability in its rate of spread, which could be due largely to differences in the invasive potential of the tumor cells. The degradation of the basal lamina and stromal extracellular matrix is mediated in part by the secretion of matrix metalloproteinases (MMPs). Matrilysin (PUMP-1, MMP-7) and gelatinase A (M(r) 72,000 type IV collagenase, MMP-2) have been shown to be overexpressed in prostate carcinoma. We have expressed the single MMP matrilysin in the tumorigenic but nonmetastatic human prostate tumor cell line DU-145 to determine if matrilysin has a functional role in prostate tumor cell invasion. DU-145 cells expressing matrilysin were significantly more invasive than vector-only transfected cell lines as assayed by a severe combined immunodeficient mouse model of tumor cell invasion. Vector-only transfected DU-145 cells injected i.p. into severe combined immunodeficient mice invaded the diaphragm in only 1 of 9 mice (11%), whereas matrilysin-transfected DU-145 cells invaded the diaphragm in 12 of 18 mice (66%). The difference between the controls and matrilysin-transfected cells was statistically significant (P < 0.006). These results suggest a functional role for matrilysin in the initial invasion of prostate cancer through the epithelial basal lamina and into the surrounding stroma.