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Extracellular matrix protein 1 (ECM1) has angiogenic properties and is expressed by breast tumor cells

ZEQIU HAN^*,1, JIAN NI^,1, PATRICK SMITS^**,1, CHARLES B. UNDERHILL^*, BIN XIE^*, YIXIN CHEN, NINGFEI LIU^*, PRZEMKO TYLZANOWSKI^¶, DAVID PARMELEE, PING FENG, IVAN DING, FENG GAO^*, REINER GENTZ, DANNY HUYLEBROECK^¶, JOZEF MERREGAERT^**,2 and LURONG ZHANG^*,23

^* Department of Oncology, Georgetown University Medical Center, Washington, D.C. 20007, USA;
Human Genome Sciences, Rockville, Maryland 20850, USA;
Department of Radiology, Rochester University Medical Center, Rochester, New York 14642, USA;
Department of Biology, Xiamen University, China;
^¶ Laboratory of Molecular Biology (Celgen) and Department of Cell Growth, Differentiation and Development, Flanders Interuniversity Institute of Biotechnology (VIB), University of Leuven, Leuven, Belgium; and
^** Laboratory of Molecular Biotechnology, Department of Biochemistry, Universiteitsplein 1, Wilrijk, Belgium

³Correspondence: Department of Oncology, Georgetown University Medical Center, 3970 Reservoir Road, NW, Washington, D.C. 20007, USA. E-mail: zhangl{at}georgetown.edu

Tumor growth and metastasis are critically dependent on the formation of new blood vessels. The present study found that extracellular matrix protein 1 (ECM1), a newly described secretory glycoprotein, promotes angiogenesis. This was initially suggested by in situ hybridization studies of mouse embryos indicating that the ECM1 message was associated with blood vessels and its expression pattern was similar to that of flk-1, a recognized marker for endothelium. More direct evidence for the role of ECM1 in angiogenesis was provided by the fact that highly purified recombinant ECM1 stimulated the proliferation of cultured endothelial cells and promoted blood vessel formation in the chorioallantoic membrane of chicken embryos. Immunohistochemical staining with specific antibodies indicated that ECM1 was expressed by the human breast cancer cell lines MDA-435 and LCC15, both of which are highly tumorigenic. In addition, staining of tissue sections from patients with breast cancer revealed that ECM1 was present in a significant proportion of primary and secondary tumors. Collectively, the results of this study suggest that ECM1 possesses angiogenic properties that may promote tumor progression.—Han, Z., Ni, J., Smits, P., Underhill, C. B., Xie, B., Chen, Y., Liu, N., Tylzanowski, P., Parmelee, D., Feng, P., Ding, I., Gao, F., Gentz, R., Huylebroeck, D., Merregaert, J., Zhang, L. Extracellular matrix protein 1 (ECM1) has angiogenic properties and is expressed by breast tumor cells.

Key Words: angiogenesis • breast cancer • ECM1 • endothelial cells

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