IngentaConnect Involvement of E-cadherin, -catenin, Cdc42 and CXCR4 in the progr...

Authors: Tucci, M.G.; Lucarini, G.¹; Brancorsini, D.¹; Zizzi, A.²; Pugnaloni, A.²; Giacchetti, A.; Ricotti, G.; Biagini, G.²

Source: British Journal of Dermatology, Volume 157, Number 6, December 2007 , pp. 1212-1216(5)

Publisher: Blackwell Publishing

Abstract:

Summary Background

A key event in cancer metastasis is the migration of tumour cells from their original location to a secondary site. The development of melanoma may be viewed as a consequence of the disruption of homeostatic mechanisms in the skin of the original site. Objectives

To investigate whether dysregulation of cell motility (Cdc42 expression), escaping the control of cell-cell and cell-matrix interactions (E-cadherin, β-catenin expression), enhances melanoma progression, and whether chemokine receptors (CXCR4) mediate cell migration and activation during invasion and metastasis development. Methods

The immunohistochemical expression of Cdc42, E-cadherin, β-catenin and CXCR4 was investigated in 30 patients with surgically treated nodular melanoma, 18 alive and disease free and 12 with a fatal outcome due to metastatic disease. Results

E-cadherin expression was significantly reduced (P < 0·05) and cytoplasmic β-catenin was increased in the patients who had died compared with disease-free individuals, while membrane expression of β-catenin was similar in the two groups. Patients with fatal outcome had increased Cdc42 (P < 0·01) and CXCR4 (P < 0·05). In this group a positive correlation was found between melanocytic Cdc42 expression and Breslow thickness (r = 0·598, P < 0·05) and between CXCR4 expression and Breslow thickness (r = 0·583, P < 0·05). Conclusions

Findings suggest that primary cutaneous melanoma with a high Breslow thickness is characterized by tumour cells with high motility and invasion ability, in line with the hypothesis that low E-cadherin levels and overexpression of Cdc42 and CXCR4 could be prognostic markers of poor outcome.

Keywords: β-catenin; Cdc42; cutaneous melanoma; CXCR4; E-cadherin

Document Type: Research article

DOI: 10.1111/j.1365-2133.2007.08246.x

Affiliations: 1: Dipartimento di Neuroscienze, Istituto di Anatomia Patologica, Azienda Ospedaliero-Universitaria, Ospedali Riuniti Lancisi-Salesi-Umberto I, Via Conca 71, 60020 Torrette, Ancona, Italy 2: Istologia-Dipartimento di Patologia Molecolare e Terapie Innovative, Università Politecnica delle Marche, Via Tronto 10/A, 60020 Torrette, Ancona, Italy

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Involvement of E-cadherin, β-catenin, Cdc42 and CXCR4 in the progression and prognosis of cutaneous melanoma