P-cadherin promotes cell-cell adhesion and counteracts invasion in human melanoma.
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.
Van Marck
Veerle
V
Laboratory of Experimental Cancerology, Department of Radiotherapy and Nuclear Medicine, Ghent University Hospital, Ghent, Belgium.
Stove
Christophe
C
Van Den Bossche
Karolien
K
Stove
Veronique
V
Paredes
Joana
J
Vander Haeghen
Yves
Y
Bracke
Marc
M
D000818:Animals; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051177:Catenins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D002645:Chickens; D006801:Humans; D007365:Intercellular Junctions / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D017434:Protein Structure, Tertiary; D014161:Transduction, Genetic
D015820:Cadherins; D051177:Catenins