The
lysyl oxidase gene family members function as extracellular matrix modulating
enzymes. We have found that a member of this family, lysyl oxidase related
protein-1 (LOR-1), is highly expressed in metastatic breast cancer derived cell
lines but not in the non-metastatic estrogen dependent MCF-7 cells. Furthermore,
LOR-1 expression in periductal tumor cells of breast carcinomas is significantly
correlated with increased tumor malignancy. MCF-7 cells expressing recombinant
LOR-1 formed estrogen dependent tumors that developed much slower than tumors
derived from empty vector transfected MCF-7 cells. The cells of these LOR-1
expressing tumors were surrounded by a high concentration of dense collagen
fibers and the tumors contained many fibrotic foci. Induction of fibrosis
in-vivo
by lysyl oxidase like enzymes has never been observed before, and
suggests that LOR-1 may function as an autonomous inducer of fibrosis. The
appearance of fibrotic foci in spontaneous breast cancer tumors is correlated
with poor prognosis and metastasis, and we therefore examined the invasiveness
of the LOR-1 expressing tumors. LOR-1 expressing MCF-7 cells invaded the
pseudo-capsules surrounding the tumors. In contrast, vector transfected
MCF-7 cells did not invade the
pseudo-capsules. This observation suggests that LOR-1 enhances the malignancy of
the tumors. Furthermore, the LOR-1 expressing tumor cells invaded blood vessels,
nerves, and muscles adjacent to the tumor, indicating that the LOR-1 expressing
MCF-7 cells acquired metastatic
properties. We conclude that LOR-1 promotes tumor fibrosis and tumor
invasiveness simultaneously indicating that these two processes may be
associated.
