P-cadherin promotes cell-cell adhesion and counteracts invasion in human melanoma

被引:76
作者
Van Marck, V
Stove, C
Van Den Bossche, K
Stove, V
Paredes, J
Haeghen, YV
Bracke, M
机构
[1] Ghent Univ Hosp, Expt Cancerol Lab, Dept Radiotherapy & Nucl Med, B-9000 Ghent, Belgium
[2] Ghent Univ Hosp, Expt Cancerol Lab, Dept Dermatol, B-9000 Ghent, Belgium
[3] Ghent Univ Hosp, Expt Cancerol Lab, Clin Chem Microbiol & Immunol, B-9000 Ghent, Belgium
[4] Ghent Univ VIB, Unit Mol Cell Biol, Dept Mol Biomed Res, Ghent, Belgium
[5] Ghent Univ VIB, Unit Mol & Cellular Oncol, Dept Mol Biomed Res, Ghent, Belgium
[6] Univ Porto, Inst Pathol & Mol Immunol, P-4100 Oporto, Portugal
关键词
D O I
10.1158/0008-5472.CAN-04-4414
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Malignant transformation of melanocytes frequently coincides with alterations in epithelial cadherin (E-cadherin) expression, switching on of neural cadherin (N-cadherin), and, when progressed to a metastatic stage, loss of membranous placental cadherin (P-cadherin). In vitro studies of melanoma cell lines have shown invasion suppressor and promoter roles for E-cadherin and N-cadherin, respectively. In the present study, we investigated the effect of P-cadherin on aggregation and invasion using melanoma cells retrovirally transduced with human P-cadherin. De novo expression of P-cadherin in P-cadherin-negative cell lines (BLM and HMB2) promoted cell-cell contacts and Ca2+-dependent cell-cell aggregation in two- and three-dimensional cultures, whereas it counteracted invasion. These effects were not observed following P-cadherin transduction of endogenously P-cadherin-positive MeWo cells. In addition, P-cadherin-transduced BLM cells coaggregated with keratinocytes and showed markedly reduced invasion in a reconstructed skin model. The proadhesive and anti-invasive effects of P-cadherin were abolished on targeted mutation of its intracellular juxtamembrane domain or its extracellular domain. For the latter mutation, we mimicked a known missense mutation in P-cadherin (R503H), which is associated with congenital hypotrichosis with juvenile macular dystrophy.
引用
收藏
页码:8774 / 8783
页数:10
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