H-cadherin expression reduces invasion of malignant melanoma.
Melanocytic behavior, survival, and proliferation are regulated through a complex system of cell-cell adhesion molecules. Pathologic changes leading to development of malignant melanoma, upset the delicate homeostatic balance between melanocytes and keratinocytes and can lead to altered expression of cell-cell adhesion and cell-cell communication molecules. Malignant transformation of melanocytes frequently coincides with loss of E-cadherin expression. We now show loss of another member of the superfamily of classical cadherins, H-cadherin (CDH13), which may be involved in the development of malignant melanoma. The provided data show that H-cadherin expression is lost in nearly 80% of the analyzed melanoma cell lines. Knockdown of H-cadherin using siRNA increases invasive capacity in melanocytes. Functional assays show that the re-expression of H-cadherin decreases migration and invasion capacity, as well as anchorage-independent growth in comparison to control melanoma cells. Furthermore, melanoma cells, which re-express H-cadherin via stable transfection show a reduction in rate of tumor growth in a nu/nu mouse tumor model in comparison to the parental control transfected cell lines. Our study presents for the first time the down-regulation of H-cadherin in malignant melanomas and its possible functional relevance in maintenance healthy skin architecture.
Melanoma Genomics Group, The Queensland Institute of Medical Research, Brisbane, Qld, Australia. Silke.Kuphal@klinik.uni-regensburg.de
Silke
S
Kuphal
Adam C
AC
Martyn
Julie
J
Pedley
Lisa M
LM
Crowther
Vanessa F
VF
Bonazzi
Peter G
PG
Parsons
Anja K
AK
Bosserhoff
Nicholas K
NK
Hayward
Glen M
GM
Boyle
D000818:Animals; D001483:Base Sequence; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D019175:DNA Methylation; D020868:Gene Silencing; D006801:Humans; D008545:Melanoma / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness / Q000473:pathology; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism
D015820:Cadherins; C099972:H-cadherin; D034741:RNA, Small Interfering