This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Akiri, G. Articles by Neufeld, G. Search for Related Content PubMed PubMed Citation Articles by Akiri, G. Articles by Neufeld, G.

Lysyl Oxidase-related Protein-1 Promotes Tumor Fibrosis and Tumor Progression in Vivo¹

Department of Cell Biology and Anatomy, The Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, 31096, Israel [G. A., Z. V., Y. K., N. G., O. K., G. N.]; Department of Pathology, Carmel Medical Center, Haifa, 34632, Israel [E. S., M. R.]; Department of Biological Regulation, Weizmann Institute of Science, Rehovot, 76100, Israel [H. D., M. N.]; and Laboratory of Molecular and Cellular Cardiology, Department of Cardiology, Carmel Medical Center, Haifa, 34632, Israel [T. C.]

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.

This article has been cited by other articles:

				H. Peinado, G. Moreno-Bueno, D. Hardisson, E. Perez-Gomez, V. Santos, M. Mendiola, J. I. de Diego, M. Nistal, M. Quintanilla, F. Portillo, et al. Lysyl Oxidase-Like 2 as a New Poor Prognosis Marker of Squamous Cell Carcinomas Cancer Res., June 15, 2008; 68(12): 4541 - 4550. [Abstract] [Full Text] [PDF]

				C. Guruvayoorappan and G. Kuttan Biophytum sensitivum (L.) DC Inhibits Tumor Cell Invasion and Metastasis Through a Mechanism Involving Regulation of MMPs, Prolyl Hydroxylase, Lysyl Oxidase, nm23, ERK-1, ERK-2, STAT-1, and Proinflammatory Cytokine Gene Expression in Metastatic Lung Tissue Integr Cancer Ther, March 1, 2008; 7(1): 42 - 50. [Abstract] [PDF]

				G. Wu, Z. Guo, X. Chang, M. S. Kim, J. K. Nagpal, J. Liu, J. M. Maki, K. I. Kivirikko, S. P. Ethier, B. Trink, et al. LOXL1 and LOXL4 Are Epigenetically Silenced and Can Inhibit Ras/Extracellular Signal-Regulated Kinase Signaling Pathway in Human Bladder Cancer Cancer Res., May 1, 2007; 67(9): 4123 - 4129. [Abstract] [Full Text] [PDF]

				S.-L. Lin, D. Chang, and S.-Y. Ying Hyaluronan stimulates transformation of androgen-independent prostate cancer Carcinogenesis, February 1, 2007; 28(2): 310 - 320. [Abstract] [Full Text] [PDF]

				O. Aprelikova, M. Wood, S. Tackett, G. V.R. Chandramouli, and J. C. Barrett Role of ETS Transcription Factors in the Hypoxia-Inducible Factor-2 Target Gene Selection Cancer Res., June 1, 2006; 66(11): 5641 - 5647. [Abstract] [Full Text] [PDF]

				C. Bouez, C. Reynaud, E. Noblesse, A. Thepot, C. Gleyzal, J. Kanitakis, E. Perrier, O. Damour, and P. Sommer The Lysyl Oxidase LOX Is Absent in Basal and Squamous Cell Carcinomas and Its Knockdown Induces an Invading Phenotype in a Skin Equivalent Model Clin. Cancer Res., March 1, 2006; 12(5): 1463 - 1469. [Abstract] [Full Text] [PDF]

				M. EGEBLAD, L.E. LITTLEPAGE, and Z. WERB The Fibroblastic Coconspirator in Cancer Progression Cold Spring Harb Symp Quant Biol, January 1, 2005; 70(0): 383 - 388. [Abstract] [PDF]

				F. M. Fennessy, K. J. Mortele, T. Kluckert, A. Gogate, S. Ondategui-Parra, P. Ros, and S. G. Silverman Hepatic Capsular Retraction in Metastatic Carcinoma of the Breast Occurring with Increase or Decrease in Size of Subjacent Metastasis Am. J. Roentgenol., March 1, 2004; 182(3): 651 - 655. [Abstract] [Full Text] [PDF]