Expression of lumican, a small leucine-rich proteoglycan with antitumour activity, in human malignant melanoma

Abstract

We showed that lumican and decorin are located in the dermis and in the peritumoral stroma of malignant melanoma, but are not found in melanoma cells or dense tumour tissue. In the healthy dermis, distant from the tumour, the increasing ratio of lumican to decorin was inversely correlated with the proliferation of the tumour cells (P = 0.035). The comparison of the level of expression of lumican protein in superficial vs. nodular subtypes of malignant melanomas showed a decrease of lumican but not decorin in the peritumoral stroma of nodular subtypes. In the peritumoral stroma, the level of expression of lumican but not decorin decreased significantly (P = 0.016) with increasing Clark levels. In addition, immunocytochemical and reverse transcription PCR analyses of malignant melanoma cell lines (A-375, HT-144) and of MRC-5 and dermal fibroblasts from healthy donors in vitro confirmed that dermal fibroblasts are responsible for lumican and decorin synthesis in skin. CONCLUSIONS. Lumican may regulate vertical progression of human malignant melanoma, but further study is necessary to clarify the antitumour mechanism and the downstream signal transduction pathways involved.

HER-2/neu-mediated Down-regulation of Biglycan Associated with Altered Growth Properties

“…Transgenic overexpression of Bgn inhibited the HER-2/neuinduced cell proliferation, anchorage-independent growth on poly-Heme-coated cell culture dishes, and migration. This is in line with previous reports demonstrating that the SLRPs lumican and decorin (14,18,43) suppress the oncogene-mediated transformation process. Overexpression of these molecules not only inhibit the proliferation of transformed cells in vitro but also their tumorigenicity in vivo.…”

“…Most of the studies have focused on the SLRPs lumican and decorin, which are typically located around the tumor microenvironment and have been shown to possess antitumor activity. Whereas lumican blocks melanoma progression by regulation of cell migration, proliferation, and induction of apoptosis (13,14), decorin represents a powerful cell growth and migration inhibitor by modulating tumor stroma deposition and cell signaling pathways including a reduced cyclin-dependent kinase and TGF-␤ activity (15,16).…”

Lumican affects actin cytoskeletal organization in human melanoma A375 cells

“…Overexpression of lumican mRNA has been reported in pancreatic cancer tissue, distinguishing it from normal pancreas (Koninger et al, 2004). This protein has recently been shown in the dermis and peritumoral stroma of malignant melanoma (Brézillon et al, 2007) and in in vitro cultured melanoma cell lines, but not in normal melanocytes (Sifaki et al, 2006).…”

Lumican Reduces Tumor Growth Via Induction of Fas-Mediated Endothelial Cell Apoptosis

“…Immunohistochemical (IHC) analysis of lumican expression has been reported in melanoma, breast, pancreatic, colorectal, cervical, neuroendocrine, and lung carcinomas [9][10][11][12][13][14]. Similarly, microarray studies have highlighted trends in lumican mRNA expression in various stages of these and other cancer types.…”