Role for connexin 26 in metastasis of human malignant melanoma: communication between melanoma and endothelial cells via connexin 26.
BACKGROUND
Connexins form the intercellular channels of the gap junction and play an integral part in a variety of biological functions, such as maintaining tissue homeostasis, cell growth control, and development. Previously it was demonstrated that the expression of connexin 26 (Cx26) can increase the metastatic potential of mouse melanoma cells. The objective of the study was to investigate the role Cx26 plays in the metastasis of human melanoma cells, focusing on the communication between melanoma cells and endothelial cells.


METHODS
Immunostaining was used to examine Cx26 expression in the melanoma lesions and in the endothelial cells around the melanoma cell nests. In all, 33 melanomatous tissue samples from 16 patients were studied, as well as nevocellular nevus (NCN) and normal skin samples. Cx26 mRNA and protein expression was also examined in the cultured endothelial cells. A dye-transfer assay was performed to examine gap junction formation between melanoma cells and endothelial cells.


RESULTS
Immunohistochemistry demonstrated that Cx26 was clearly expressed by the endothelial cells of the small vessels surrounding the melanoma cell nests as well as the melanoma cells. Cx26 mRNA and protein expression was detected in cultured endothelial cells. In a coculture system with human malignant melanoma cell line (HMY-1) and endothelial cells (HMVEC), immunohistochemistry indicated Cx26 expression in both types of cells and dye-transfer assay demonstrated dye-coupling from HMY-1 into HMVEC.


CONCLUSIONS
Cx26 may contribute to the metastasis of melanoma by facilitating communication between melanoma cells and their surrounding endothelial cells.
Saito-Katsuragi
Mamiko
M
Department of Dermatology, Nara Medical University, Kashihara, Nara, Japan.
Asada
Hideo
H
Niizeki
Hironori
H
Katoh
Fumitaka
F
Masuzawa
Mikio
M
Tsutsumi
Masahiro
M
Kuniyasu
Hiroki
H
Ito
Akihiko
A
Nojima
Hiroshi
H
Miyagawa
Sachiko
S
D000328:Adult; D000368:Aged; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D000072259:Connexin 26; D000075302:Connexin 30; D017630:Connexins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
D000075302:Connexin 30; D017630:Connexins; C000607042:GJB2 protein, human; C491020:GJB6 protein, human; C000607043:Gjb2 protein, mouse; D012333:RNA, Messenger; D000072259:Connexin 26