Miyazaki K, Koshikawa N, Hasegawa S, Momiyama N, Nagashima Y, Moriyama K, Ichikawa Y, Ishikawa T, Mitsuhashi M, Shimada H
Division of Cell Biology, Kihara Institute for Biological Research, Yokohama City University, Yokohama, Japan.
Cancer Chemother Pharmacol. 1999;43 Suppl:S52-5. doi: 10.1007/s002800051098.
Matrilysin (MMP-7) is the smallest member of the matrix metalloproteinase (MMP) family. It is frequently expressed in various types of cancer including colon, stomach, prostate, and brain cancers. Previous studies have suggested that matrilysin plays important roles in the progression and metastasis of colon cancer. Recently, we have examined the effects of a matrilysin-specific antisense phosphorothioate oligodeoxyribonucleotide on in vitro invasion and liver metastasis in nude mice of two human colon carcinoma cell lines (CaR-1 and WiDr). In culture, the antisense oligonucleotide effectively inhibited both the secretion of matrilysin by CaR-1 cells and their in vitro invasion through a reconstituted basement membrane. In a nude mouse model, the antisense oligonucleotide potently suppressed the experimental liver metastasis of WiDr cells from the spleen. These results suggest that matrilysin has an important role in the liver metastasis of human colon cancer and that matrilysin antisense oligonucleotides have therapeutic potential for the prevention of metastasis.
基质溶素(MMP - 7)是基质金属蛋白酶(MMP)家族中最小的成员。它在包括结肠癌、胃癌、前列腺癌和脑癌在内的多种癌症类型中频繁表达。先前的研究表明,基质溶素在结肠癌的进展和转移中起重要作用。最近,我们研究了一种基质溶素特异性反义硫代磷酸酯寡脱氧核糖核苷酸对两种人结肠癌细胞系(CaR - 1和WiDr)体外侵袭和裸鼠肝转移的影响。在培养中,反义寡核苷酸有效抑制了CaR - 1细胞基质溶素的分泌及其通过重组基底膜的体外侵袭。在裸鼠模型中,反义寡核苷酸有力地抑制了WiDr细胞从脾脏向肝脏的实验性转移。这些结果表明,基质溶素在人结肠癌肝转移中起重要作用,并且基质溶素反义寡核苷酸具有预防转移的治疗潜力。