Expression of fibrogenic cytokines in desmoplastic malignant melanoma

Abstract

Desmoplastic malignant melanoma (DMM) consists of amelanotic spindle-shaped melanoma cells and is accompanied by desmoplasia with fibrous stromata. It has a strong tendency for local infiltrative growth and recurrence and a propensity for neurotropism. It is not yet known which cytokine is responsible for the desmoplasia in DMM. In the present study, we investigated the roles of several fibrogenic cytokines and cytokine receptors in DMM: basic fibroblast growth factor (bFGF), connective tissue growth factor (CTGF), transforming growth factor-beta, platelet-derived growth factor (PDGF) and PDGF receptors. Immunostaining and in situ hybridization were conducted in four cases of DMM and four cases of amelanotic malignant melanoma (AMM) as negative controls for desmoplasia. PDGF-beta receptor, bFGF and CTGF were intensely expressed in the DMM specimens in comparison with the AMM specimens. The reaction of PDGF-B ligand and CTGF to PDGF-beta receptor, in addition to the expression of bFGF, may contribute to the desmoplasia in DMM.

Connective Tissue Growth Factor Confers Drug Resistance in Breast Cancer through Concomitant Up-regulation of Bcl-xL and cIAP1

“…CTGF is a secreted growth factor that can bind to integrins on the cell surface (3) and also serves as an angiogenic factor in collaboration with matrix metalloproteinases (4). Elevated CTGF expression has been observed in breast cancers (5), pancreatic cancers (6), melanomas (7), and chondrosarcomas (8). Although CTGF shows multiple roles in various cancer types, in breast tumor cells CTGF overexpression has been linked to tumor size increase and lymph node metastasis (5,9).…”

Expressions of cysteine-rich61, connective tissue growth factor and Nov genes in hepatocellular carcinoma and their clinical significance

“…In addition to contributing to TGF-β-mediated AIG, CTGF could interact synergistically with EGF, PDGF, IGF-I, or bFGF, suggesting that it activates the receptors and/or signaling pathways used by other growth factors [28,29] . Consistent with its profibrotic properties, CTGF has been found to be overexpressed in pancreatic cancers, mammary tumors, and melanomas [30][31][32] . In our study, the expression of CTGF gene in HCC tissue was obviously higher than that in paracancerous normal liver tissues, indicating that CTGF might play an important role in hepatocellular carcinogenesis.…”

Identification of an RNA element that confers post-transcriptional repression of connective tissue growth factor/hypertrophic chondrocyte specific 24 (ctgf/hcs24) gene: Similarities to retroviral RNA-protein interactions

“…Therefore, disabling the repression machinery to lead to consititutive CTGF expression may well cause or assist in a discontrolled status such as ®brosis and oncogenesis (Mori et al, 1999). This idea is actually well-represented by the fact that strong CTGF expression is observed in malignant tumor cells of di erent origins including chondrocytes and melanocytes (Kubo et al, 1998). In this study, we discovered an element that contributes a repressive mode to the ctgf gene.…”