sFRP-1 binds via its netrin-related motif to the N-module of thrombospondin-1 and blocks thrombospondin-1 stimulation of MDA-MB-231 breast carcinoma cell adhesion and migration.

Abstract

Secreted frizzled-related protein (sFRP)-1 is a Wnt antagonist that inhibits breast carcinoma cell motility, whereas the secreted glycoprotein thrombospondin-1 stimulates adhesion and motility of the same cells. We examined whether thrombospondin-1 and sFRP-1 interact directly or indirectly to modulate cell behavior. Thrombospondin-1 bound sFRP-1 with an apparent K(d)=48nM and the related sFRP-2 with a K(d)=95nM. Thrombospondin-1 did not bind to the more distantly related sFRP-3. The association of thrombospondin-1 and sFRP-1 is primarily mediated by the amino-terminal N-module of thrombospondin-1 and the netrin domain of sFRP-1. sFRP-1 inhibited α3β1 integrin-mediated adhesion of MDA-MB-231 breast carcinoma cells to a surface coated with thrombospondin-1 or recombinant N-module, but not adhesion of the cells on immobilized fibronectin or type I collagen. sFRP-1 also inhibited thrombospondin-1-mediated migration of MDA-MB-231 and MDA-MB-468 breast carcinoma cells. Although sFRP-2 binds similarly to thrombospondin-1, it did not inhibit thrombospondin-1-stimulated adhesion. Thus, sFRP-1 binds to thrombospondin-1 and antagonizes stimulatory effects of thrombospondin-1 on breast carcinoma cell adhesion and motility. These results demonstrate that sFRP-1 can modulate breast cancer cell responses by interacting with thrombospondin-1 in addition to its known effects on Wnt signaling.

• Authors: Gema Martin-Manso, Maria J Calzada, Yoshiro Chuman, John M Sipes, Charles P Xavier, Vladimir Wolf, Svetlana A Kuznetsova, Jeffrey S Rubin, David D Roberts
• Journal: Archives of biochemistry and biophysics (Arch Biochem Biophys) Vol. 509 Issue 2 Pg. 147-56 (May 15 2011) ISSN: 1096-0384 [Electronic] United States
• PMID: 21402050 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
• Copyright: Published by Elsevier Inc.

Chemical References

• Glycoproteins
• Intercellular Signaling Peptides and Proteins
• Intracellular Signaling Peptides and Proteins
• Membrane Proteins
• SFRP1 protein, human
• SFRP2 protein, human
• Thrombospondin 1
• WD repeat containing planar cell polarity effector
• Nerve Growth Factor

Topics

• Amino Acid Motifs
• Breast (metabolism, pathology)
• Breast Neoplasms (metabolism, pathology)
• Cell Adhesion
• Cell Line, Tumor
• Female
• Glycoproteins (metabolism)
• Humans
• Intercellular Signaling Peptides and Proteins (chemistry, metabolism)
• Intracellular Signaling Peptides and Proteins
• Membrane Proteins (chemistry, metabolism)
• Nerve Growth Factor (chemistry)
• Thrombospondin 1 (chemistry, metabolism)