Ah. Ree et al., REGULATION OF TISSUE-DEGRADING FACTORS AND IN-VITRO INVASIVENESS IN PROGRESSION OF BREAST-CANCER CELLS, Clinical & experimental metastasis, 16(3), 1998, pp. 205-215
Hormone-independent growth and invasiveness represent phenotypic prope
rties acquired during early progression of breast cancer. We compared
human mammary adenocarcinoma cells, MCF-7, which are estrogen-dependen
t and poorly metastatic, with the estrogen-independent and highly meta
static subline, MCF7/LCC1, with regard to expression of tissue-degradi
ng factors of the matrix metalloproteinase (MMP)- and urokinase (uPA)-
dependent degradative pathways, as well as for their in vitro invasive
properties, Both cell lines showed low constitutive mRNA expression o
f the MMP inhibitor TIMP-1. Baseline expression of TIMP-2 mRNA was als
o very low in MCF-7 cells, whereas the MCF7/LCC1 level was much higher
(similar to 10-fold). Furthermore, both cell lines revealed low const
itutive capacity to migrate in an in vitro invasion assay. Treatment w
ith 12-O-tetradecanoylphorbol-13-acetate (TPA; 100 nM) induced the mRN
As for TIMP-1. as well as for MMP-1, MMP-9, the uPA receptor, and the
uPA inhibitor PAI-1, amongst which only the responses of MMP-9 and PAI
-1 were cell-specific. The mRNA levels of MMP-9 and PAI-1 were similar
to 10-fold and similar to 15-fold higher in MCF7/LCC1 cells compared
to MCF-7 cells. The secretion of immunoreactive PAI-1 was considerably
elevated (> 20-fold) in TPA-treated MCF7/LCC1 cells, whereas the TPA-
dependent level of 92-kDa MMP-9 was only similar to 2-fold higher in M
CF7/LCC1 cells than in MCF-7 cells, In both cell lines treatment with
TPA was associated with an increase (similar to 10-fold) in in vitro m
igration, which. in the MCF7/LCC1 cells was significantly attenuated b
y a reconstituted basement membrane extract (Matrigel). These data sug
gest that TPA-responsive in vitro invasive properties that are probabl
y associated with PAI-1 expression may co-vary with progression from h
ormone-dependent to -independent breast cancer. (C) 1998 Lippincott-Ra
ven Publishers.