ENHANCEMENT OF TYPE-IV COLLAGENASES BY HIGHLY METASTATIC VARIANTS OF HT1080 FIBROSARCOMA CELLS ESTABLISHED BY A TRANSENDOTHELIAL INVASION SYSTEM IN-VITRO

A novel in vitro invasion assay system was established in this laborat ory, in which the invasion of tumor cells after interaction with endot helial cells could be examined, Two variant cell lines (FP-10, FP-21) were established from parental HT1080 cells using this assay system. F P-10 and FP-21 cells had higher invasive and metastatic potential than the parental cells both in vitro and in vivo. The activity of anchora ge-independent proliferation and the adhesion to the HUVEC monolayer o f FP-10 and FP-21 was greater than the parental cells, The secretion o f type TV collagenase (both MMP-2 and MMP-9) was also increased more s ignificantly by the variant cells than by the parental cells, and the expression of uPA mRNA was higher in FP-10 and FP-21. Treatment of var iant cells with human TIMP-2 remarkably suppressed the increment of th e in vitro invasion to the same level as parental cells, These results suggest that this in vitro transendothelial invasion system accelerat es multiple mechanisms of the metastasis by HT1080, especially the pro duction of type TV collagenases, It can thus provide a useful model of tumor metastasis. (C) 1998 Lippincott-Raven Publishers.