Data from Matricellular Protein WISP2 Is an Endogenous Inhibitor of Collagen Linearization and Cancer Metastasis

• DOI: 10.1158/0008-5472.c.6513000
• Publication Date: 2023-03-31T06:39:24Z
• Authors: Jagadeesh Janjanam; Glendin Pano; Ruishan Wang; Benjamin A. Minde...; Hannah Breeze-Jones; Eleanor Baker; Cecile Garcin; Georgia Clayton; Abbas Shirinifard; Ana Maria Zaske; David Finkelstein; Myriam Labelle
• Keywords: Matricellular protein

<div>Abstract<p>Collagen remodeling contributes to many physiologic and pathologic processes. In primary tumors, the linearization of collagen fibers promotes cancer cell invasion metastasis is indicative poor prognosis. However, it remains unknown whether there are endogenous inhibitors that could be exploited therapeutically. Here, we show controlled by two secreted matricellular proteins with antagonistic functions. Specifically, WISP1 was cells, bound type I (Col I), linearized Col via its cysteine-rich C-terminal (CT) domain. contrast, WISP2, which lacks a CT domain, inhibited preventing WISP1-Col binding. Analysis patient data revealed <i>WISP2</i> expression lower in most solid comparison normal tissues. Consequently, genetic or pharmacologic restoration higher WISP2 levels impaired prevented tumor <i>in vivo</i> models human murine breast cancer. Thus, this study uncovers as first inhibitor ever identified reveals architecture can normalized therapeutically restoring high WISP2:WISP1 ratio.</p>Significance:<p>Two factors, antagonistically regulate linearization, increasing ratio tumors limits inhibits metastasis.</p><p><i>See related commentary Barcus Longmore, p. 5611</i></p></div>