Overexpression of Hsp27 in a human melanoma cell line: regulation of E-cadherin, MUC18/MCAM, and plasminogen activator (PA) system

Abstract

Hsp27 is considered a potential marker for cell differentiation in diverse tissues. Several aspects linked to the differentiation process and to the transition from high to low metastatic potential were analyzed in melanoma cells transfected with Hsp27. E-cadherin plays a central role in cell differentiation, migration, and normal development. Loss of expression or function of E-cadherin has been documented in a variety of human malignancies. We observed by fluorescence-activated cell sorter (FACS) as well as immunofluorescence (IF) analysis a pronounced expression of E-cadherin in Hsp27-transfected A375 melanoma cells compared with control melanoma cells. The expression of the adhesion molecule MUC18/MCAM correlates directly with the metastatic potential of melanoma cells. In contrast to wild-type and neotransfected melanoma cells, in Hsp27-transfected cells the expression of MUC18/MCAM could not be detected by FACS and IF analysis. The plasminogen activator (PA) system plays a central role in mediating extra-cellular proteolysis and also in nonproteolytic events such as cell adhesion, migration, and transmembrane signaling. Hsp27 transfectants revealed elevated messenger ribonucleic acid expression of the urokinase-type PA (uPA) and its inhibitor, PA inhibitor type 1, which might indicate a neutralization effect of the proteolytic activity of uPA. Control cells failed to express both these molecules. The influence of Hsp27 expression on uPA activity and the involvement of E-cadherin could be demonstrated by use of anti-E-cadherin-blocking antibody. Our data provide evidence for an inhib-itory-regulatory role of Hsp27 in tumor progression as found in our system.

HSP27 is involved in the pathogenesis of kidney tubulointerstitial fibrosis

“…Double bands on immunoblots (Fig. 5A) are consistent with previously reported in vitro and animal studies and are probably related to the phosphorylation state of HSP27 (1,6,19). We next used this dose of TGF-␤1 and examined the expression of HSP27 and its signaling pathway during TGF-␤1-induced EMT.…”

“…Immunofluorescence studies were in concert with these findings showing costaining of E-cadherin and HSP27 in TGF-␤1-treated cells and the UUO model, indicating that HSP27 may interact with E-cadherin during EMT and tubulointerstitial fibrosis. Indeed, recent data support this hypothesis by demonstrating a dialog between HSP27 and adherens junction/focal adhesion (1,9,44). For example, overexpression of HSP27 in human melanoma cell lines upregulated E-cadherin while decreasing matrix metalloproteinases 2 and 9 and tumor markers MUC18/MCAM, suggesting an inhibitory-regulatory role for HSP27 in melanoma progression (1).…”

“…Indeed, recent data support this hypothesis by demonstrating a dialog between HSP27 and adherens junction/focal adhesion (1,9,44). For example, overexpression of HSP27 in human melanoma cell lines upregulated E-cadherin while decreasing matrix metalloproteinases 2 and 9 and tumor markers MUC18/MCAM, suggesting an inhibitory-regulatory role for HSP27 in melanoma progression (1). Conversely, desmosome signaling may also activate HSP27 (9).…”

The major vault protein is responsive to and interferes with interferon-γ-mediated STAT1 signals

“…Expressions of multiple cell surface marker proteins were determined by flow cytometry as described (Aldrian et al, 2003;Steinberger et al, 2004) using the mouse monoclonal antibodies 5-92 (CD13), 5-390 (CD13), 5-271 (CD36), VIAP (isotype control) (all supplied by O. Majdic, Institute of Immunology, Vienna), and ICAM-1 (Biodesign, Saco, ME).…”

Hsp-27 Expression in Invasive Ductal Breast Carcinoma

“…High expression of Hsp27 has been found to correlate with resistance to cisplatin, doxorubicin and other anticancer drugs used in breast cancer chemotherapy [11]. The expression of Hsp27 decreases the metastatic potential by increasing the expression of E-cadherin and decreasing the expression of MCAM/MUC18 (MCAM, melanoma cell adhesion molecule) in melanoma cells [12].…”