Matrix metalloproteinases (MMPs) play an essential role in remodeling of extracellular matrices (ECMs) involved in various biological processes, such as inflammation, tissue regeneration and tumor invasion. Among the MMPs, gelatinase A (MMP-2) is the most abundant MMP and frequently correlates with malignant progression and invasive behavior of tumor cells [
1].
In situ hybridization studies of human surgical specimens have shown that stromal fibroblasts are the predominant source of MMP-2 in the majority of carcinomas [
2‐
4]. Malignant cells stimulate nearby fibroblasts to produce MMPs via soluble cytokines and growth factors or through cell surface interactions mediated by plasma membrane proteins, such as emmprin [
5]. Emmprin, also known as basigin/CD147, is an integral plasma membrane glycoprotein of the Ig superfamily that contains two extracellular Ig domains [
6]. Expression of emmprin is upregulated in human malignant tumors, such as breast, lung and bladder carcinomas, malignant melanomas, gliomas and lymphomas, compared with their normal counterparts [
7‐
11]. In malignant tumors, emmprin acts as a modulator of tumor-stroma cross-talk, since it mediates not only MMP production but also tumor angiogenesis through the stimulation of vascular endothelial growth factor (VEGF) expression [
12], induction of activated stromal myofibroblasts [
13], and anchorage-independent growth and multidrug resistance in a hyaluronan-dependent fashion [
14‐
16]. The activity-blocking monoclonal antibody (mAb), E11F4, recognizes the first Ig domain (ECI) of emmprin, implying that this region of emmprin contains the structure responsible for the activity of this protein [
5,
6]. Moreover, it is reported that emmprin-induced stimulation of MMP production in fibroblasts is dependent on N-glycosylation of its extracellular domains [
17,
18]. However, it has been reported recently that nonglycosylated recombinant emmprin could stimulate fibroblasts to express the mRNAs of MMP-1, 2 and 3 [
19]. The objective of the present study was to determine whether the activity of synthetic emmprin ECI peptides, with or without a chitobiose unit (GlcNAc-GlcNAc), the disaccharide with which N-glycosylation starts, mimics that of emmprin. The results showed that synthetic ECI substituted with a chitobiose unit, but not ECI alone, stimulates fibroblasts to produce MMP-2.