Sulf-2, a proangiogenic heparan sulfate endosulfatase, is upregulated in breast cancer.

Abstract

Sulf-2 is an endosulfatase with activity against glucosamine-6-sulfate modifications within subregions of intact heparin. The enzyme has the potential to modify the sulfation status of extracellular heparan sulfate proteoglycan (HSPG) glycosaminoglycan chains and thereby to regulate interactions with HSPG-binding proteins. In the present investigation, data mining from published studies was employed to establish Sulf-2 mRNA upregulation in human breast cancer. We further found that cultured breast carcinoma cells expressed Sulf-2 mRNA and released enzymatically active proteins into conditioned medium. In two mouse models of mammary carcinoma, Sulf-2 mRNA was upregulated in comparison to its expression in normal mammary gland. Although mRNA was present in normal tissues, Sulf-2 protein was undetectable; it was, however, detected in some premalignant lesions and in tumors. The protein was localized to the epithelial cells of the tumors. In support of the possible mechanistic relevance of Sulf-2 upregulation in tumors, purified recombinant Sulf-2 promoted angiogenesis in the chick chorioallantoic membrane assay.

• Authors: Megumi Morimoto-Tomita, Kenji Uchimura, Annette Bistrup, David H Lum, Mikala Egeblad, Nancy Boudreau, Zena Werb, Steven D Rosen
• Journal: Neoplasia (New York, N.Y.) (Neoplasia) Vol. 7 Issue 11 Pg. 1001-10 (Nov 2005) ISSN: 1522-8002 [Print] United States
• PMID: 16331886 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• DNA Primers
• RNA, Messenger
• Sulfotransferases
• SULF2 protein, human
• Sulfatases
• heparan sulfate sulfatase

Topics

• Allantois (blood supply)
• Amino Acid Sequence
• Animals
• Base Sequence
• Breast Neoplasms (enzymology, genetics)
• Chick Embryo
• Chorion (blood supply)
• DNA Primers
• Female
• Gene Expression Regulation, Enzymologic
• Gene Expression Regulation, Neoplastic
• Humans
• Molecular Sequence Data
• Neovascularization, Physiologic
• Polymerase Chain Reaction (methods)
• RNA, Messenger (genetics)
• Sulfatases (genetics)
• Sulfotransferases (genetics)