Lumican Inhibits SNAIL-Induced Melanoma Cell Migration Specifically by Blocking MMP-14 Activity.

Marta Stasiak,Isabelle Proult,Corinne Perreau,Shukti Chakravarti,Stéphane Brézillon,Joanna Boncela,François-Xavier Maquart,M Anna Kowalska,Aurore Chatron-Colliet,Patrycja Przygodzka,Konstantina Karamanou,Yanusz Wegrowski

doi:10.1371/journal.pone.0150226

Abstract

Lumican, a small leucine rich proteoglycan, inhibits MMP-14 activity and melanoma cell migration in vitro and in vivo. Snail triggers epithelial-mesenchymal transitions endowing epithelial cells with migratory and invasive properties during tumor progression. The aim of this work was to investigate lumican effects on MMP-14 activity and migration of Snail overexpressing B16F1 (Snail-B16F1) melanoma cells and HT-29 colon adenocarcinoma cells. Lumican inhibits the Snail induced MMP-14 activity in B16F1 but not in HT-29 cells. In Snail-B16F1 cells, lumican inhibits migration, growth, and melanoma primary tumor development. A lumican-based strategy targeting Snail-induced MMP-14 activity might be useful for melanoma treatment.

Highlights

Lumican belongs to the family of the small leucine–rich proteoglycans (SLRP) that contribute to extracellular matrix (ECM) assembly and organization through protein:protein and/or protein: carbohydrate interactions [1,2,3]
Lumican was localized in epithelial cells with mild reactive dysplasia and fibroblasts adjacent to colon cancer cells. These findings indicate that the lumican synthesized by cancer cells, fibroblasts and epithelial cells may affect the growth of human colorectal cancer [27]
Considering the important impact of matrix metalloproteinase (MMP)-14 in tumor cell migration and malignant progression and the antimigratory and anti-tumorigenic role of lumican, we focused on the direct interaction between these two macromolecules

Summary

Introduction

Lumican belongs to the family of the small leucine–rich proteoglycans (SLRP) that contribute to extracellular matrix (ECM) assembly and organization through protein:protein and/or protein: carbohydrate interactions [1,2,3] It is expressed widely in mesenchymal connective tissues [4, 5] and present as a proteoglycan in some tissues like the cornea due to post-translational addition of keratan sulfate glycosaminoglycan side chains, or as a glycoprotein in some tissues [6, 7]. Lumican was localized in epithelial cells with mild reactive dysplasia and fibroblasts adjacent to colon cancer cells. Overexpression of lumican has been shown to affect the migration of human colon cancer cells through up regulation of gelsolin and filamentous actin reorganization [20, 21]

Objectives

Methods

Results