title: Lysyl oxidase-related protein-1 promotes tumor fibrosis and tumor progression in vivo.
abstract: The lysyl oxidase gene family members function as extracellular matrix modulating enzymes. We have found that another 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 nonmetastatic 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 pseudocapsules surrounding the tumors. In contrast, vector-transfected MCF-7 cells did not invade the pseudocapsules. 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, which indicates that these two processes may be associated.
authors.affiliation: Department of Cell Biology and Anatomy, The Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, 31096, Israel.
authors.forename: Gal
authors.initials: G
authors.lastname: Akiri
authors.forename: Edmond
authors.initials: E
authors.lastname: Sabo
authors.forename: Hagit
authors.initials: H
authors.lastname: Dafni
authors.forename: Zehava
authors.initials: Z
authors.lastname: Vadasz
authors.forename: Yelena
authors.initials: Y
authors.lastname: Kartvelishvily
authors.forename: Noga
authors.initials: N
authors.lastname: Gan
authors.forename: Ofra
authors.initials: O
authors.lastname: Kessler
authors.forename: Tzafra
authors.initials: T
authors.lastname: Cohen
authors.forename: Murray
authors.initials: M
authors.lastname: Resnick
authors.forename: Michal
authors.initials: M
authors.lastname: Neeman
authors.forename: Gera
authors.initials: G
authors.lastname: Neufeld
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D003094:Collagen / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005355:Fibrosis / Q000201:enzymology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009336:Necrosis; D009362:Neoplasm Metastasis; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D003094:Collagen; D000594:Amino Acid Oxidoreductases; C119091:LOXL2 protein, human; C485601:Loxl2 protein, mouse