טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentGal Akiri
SubjectThe Role of Lysyl Oxidase Related Protein-1 (LOR-1) in
Breast Cancer Progression
DepartmentDepartment of Biology
Supervisor Professor Emeritus Neufeld Gera


Abstract

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.