Increased expression of connexins 26 and 43 in lymph node metastases of breast cancer.
BACKGROUND
Gap junctions are intercellular channels composed of connexins, which mediate the direct passage of small molecules between neighbouring cells. They are involved in regulation of cell cycle, cell signalling, and differentiation, and probably invasion and metastasis. The role of connexins in the metastatic process is controversial, because some studies indicate that connexin expression is inversely correlated with metastatic capacity. In contrast, others demonstrate that connexins may be involved in metastasis. In addition, connexin status in breast cancer metastasis has not been widely studied.


METHODS
We evaluated by immunohistochemistry the expression of connexin 26 (Cx26) and connexin 43 (Cx43) in primary breast tumours (PTs) and matched paired metastases to lymph nodes (MLNs).


RESULTS
In PTs, we observed predominantly cytoplasmic localisation of evaluated connexins, indicating alterations in connexin expression in breast cancer cells. We demonstrated that expression of Cx26 and Cx43 was increased in MLNs compared with PTs (p<0.00001 and p<0.001, for CX26 and Cx43, respectively). In addition, Cx26 and Cx43 negative PTs developed Cx26 and Cx43 positive MLNs. Furthermore, besides increased cytoplasmic staining, enhanced membranous localisation of Cx43, typical of normal cells, was found in MLNs. Additionally, membranous Cx26 expression appeared only in metastatic breast cancer cells.


CONCLUSIONS
These findings suggest that connexins may contribute to the efficient metastasising of breast cancer to the lymph nodes.
Department of Pathology, Medical University of Bialystok, Poland.
L
L
Kanczuga-Koda
S
S
Sulkowski
A
A
Lenczewski
M
M
Koda
A
A
Wincewicz
M
M
Baltaziak
M
M
Sulkowska
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000737:chemistry*; D002294:Carcinoma, Squamous Cell / Q000737:chemistry*; D002462:Cell Membrane / Q000737:chemistry; D000072259:Connexin 26; D018031:Connexin 43 / Q000032:analysis*; D017630:Connexins / Q000032:analysis*; D003593:Cytoplasm / Q000737:chemistry; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008207:Lymphatic Metastasis; D008875:Middle Aged; D018709:Statistics, Nonparametric
D018031:Connexin 43; D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26