Dual Roles of Ascidian Chondromodulin-1: Promoting Cell Proliferation Whilst Suppressing the Growth of Tumor Cells.

Xiaoju Dou,Xiang Li,Haiyan Yu,Bo Dong

doi:10.3390/md16020059

Abstract

Chondromodulin-1 (ChM-1) is an extracellular matrix protein that plays crucial roles in tumor cell growth and angiogenesis in vertebrates and humans. ChM-1 is highly expressed in the invertebrate Ciona savignyi, a marine ascidian chosen as a model. The effect of the recombinant Ciona mature ChM-1 peptide (Cs-mChM-1) on cell proliferation, migration and angiogenesis was evaluated on cultured cells. The results revealed that low concentrations of Cs-mChM-1 (12.5 nM) promoted osteoblastic cell (MC3T3-E1) growth and protected cells from H2O2-induced damage. However, a higher concentration of Cs-mChM-1 (i.e., 500 nM) not only suppressed both growth and migration of tumor cells, including human cervical cancer (HeLa) cells and human neuroblastoma (SH-SY5Y) cells, but also significantly inhibited proliferation and angiogenesis of human umbilical vein endothelial cells (HUVECs). The expression levels of cyclinD1 and mitogen-activated protein kinase 1 (MAPK1) were slightly increased in Cs-mChM-1 treated MC3T3-E1 cells, whereas these genes decreased in treated HeLa cells, SH-SY5Y cells and HUVECs. This result indicates that Cs-mChM-1 modifies cell behavior by regulating cell cycle and cell adhesion. Thus, the present results reveal that recombinant peptides of ChM-1 from invertebrates can play a dual role in cell proliferation and migration of different cell types. The inhibition effects on tumor cell growth and angiogenesis indicate potential pharmaceutical applications for recombinant Cs-mChM-1.

Highlights

Chondromodulin-1 (ChM-1) is a glycoprotein originating from fetal bovine cartilage
Mera et al (2009) demonstrated that recombinant human ChM-1 (rhChM-1) suppresses cell proliferation by regulating protein in the tyrosine phosphatase family, which activates MAPK through rapidly accelerated threonine-protein kinase [11]. These findings indicate that ChM-1 inhibits tumor cell proliferation by suppressing cyclinD and MAPK signaling
The results in this study revealed that lower concentrations of Cs-mChM-1 promoted the growth and restored the oxidative damage of MC3T3-E1 cells, whereas higher concentrations of Cs-mChM-1 suppressed the growth and migration of human cervical cancer (HeLa) cells and SH-SY5Y cells, and significantly inhibited the growth and angiogenesis of human umbilical vein endothelial cells (HUVECs)

Summary

Introduction

Chondromodulin-1 (ChM-1) is a glycoprotein originating from fetal bovine cartilage. It has a molecular mass of 25 kDa and can be converted into a 12 kDa mature peptide at the C-terminal RERR amino acid cleavage site, subsequently secreted into the extracellular matrix (ECM) [1,2].ChM-1 is expressed in non-vascular tissues such as immature cartilage, cardiac valves, and the cornea. Chondromodulin-1 (ChM-1) is a glycoprotein originating from fetal bovine cartilage. It has a molecular mass of 25 kDa and can be converted into a 12 kDa mature peptide at the C-terminal RERR amino acid cleavage site, subsequently secreted into the extracellular matrix (ECM) [1,2]. ChM-1 is expressed in non-vascular tissues such as immature cartilage, cardiac valves, and the cornea. It is absent in the calcified cartilage of vertebrates [3,4]. As a chondrocyte growth factor, ChM-1 is responsible for maintaining cartilage integrity during osteogenesis [5]. ChM-1 is presumed to play multiple functions in different tissues

Methods

Results

Discussion

Conclusion