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

Abstract

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.

Identification of metastasis‐associated proteins in a human tumor metastasis model using the mass‐mapping technique

“…ECM1 is a secreted glycoprotein reportedly involved in bone formation [22], in endothelial cell proliferation, and in the promotion of angiogenesis [23], but its function is best studied in basement membrane physiology. ECM1 has been shown to interact specifically with perlecan, a major heparan sulfate proteoglycan of basement membranes [24] and loss of ECM1 function in humans is responsible for lipoid proteinosis, a rare, autosomal recessive skin disorder which involves widespread hyaline deposition and the disruption/reduplication of basement membranes [25].…”

“…ECM1 has been shown to interact specifically with perlecan, a major heparan sulfate proteoglycan of basement membranes [24] and loss of ECM1 function in humans is responsible for lipoid proteinosis, a rare, autosomal recessive skin disorder which involves widespread hyaline deposition and the disruption/reduplication of basement membranes [25]. Analysis of expression of ECM1 in a panel of human tumors found that it was closely correlated with some types of tumors, including breast carcinoma [23], gastric cancer and colorectal cancer. Furthermore, ECM1 expression correlated with the metastatic potential of tumors in one study.…”

Chondrocyte secretome: a source of novel insights and exploratory biomarkers of osteoarthritis

“…It is able to enhance the proliferation of endothelial cells during angiogenesis [44] and inhibit MMP-9 proteolytic activity [45]. Louridos et al observed that the level of ECM-1 secreted by cells originating from damaged OA cartilage is 3-fold higher than that of healthy cartilage [13].…”

Importance of Extracellular Matrix Protein 1 (ECM1) in Maintaining the Functional Integrity of the Human Skin

“…The biological function of ECM1 is not fully elucidated, but indications for its involvement in important processes like skin differentiation, endochondral bone formation and angiogenesis were found [5,10,11]. We have recently described the role of ECM1 in angiogenesis and its *Address correspondence to this author at the Department of Biomedical Sciences, University of Antwerp, Laboratory of Molecular Biotechnology, Campus Drie Eiken, Universiteitsplein 1, 2610 Wilrijk, Belgium; Tel: 32-3-8202311; Fax: 32-3-8202239; E-mail: joseph.merregaert@ua.ac.be implications in cancer biology [12], while its putative function in the molecular pathology of lipoid proteinosis (LiP) has been reviewed by Chan [13,33].…”