%0 Journal Article
%T Connexin-43 upregulation in micrometastases and tumor vasculature and its role in tumor cell attachment to pulmonary endothelium
%A M Khair Elzarrad
%A Abu Haroon
%A Klaus Willecke
%A Radoslaw Dobrowolski
%A Mark N Gillespie
%A Abu-Bakr Al-Mehdi
%J BMC Medicine
%D 2008
%I BioMed Central
%R 10.1186/1741-7015-6-20
%X Tumor cell attachment to pulmonary vasculature, tumor growth, and connexin-43 expression was studied in metastatic lung tumor sections obtained after tail-vein injection into nude mice of syngeneic breast cancer cell lines, overexpressing wild type connexin-43 or dominant-negatively mutated connexin-43 proteins. High-resolution immunofluorescence microscopy and Western blot analysis was performed using a connexin-43 monoclonal antibody. Calcein Orange Red AM dye transfer by fluorescence imaging was used to evaluate the gap junction function.Adhesion of breast cancer cells to the pulmonary endothelium increased with cancer cells overexpressing connexin-43 and markedly decreased with cells expressing dominant-negative connexin-43. Upregulation of connexin-43 was observed in tumor cell-endothelial cell contact areas in vitro and in vivo, and in areas of intratumor blood vessels and in micrometastatic foci.Connexin-43 facilitates metastatic 'homing' by increasing adhesion of cancer cells to the lung endothelial cells. The marked upregulation of connexin-43 in tumor cell-endothelial cell contact areas, whether in preexisting 'homing' vessels or in newly formed tumor vessels, suggests that connexin-43 can serve as a potential marker of micrometastases and tumor vasculature and that it may play a role in the early incorporation of endothelial cells into small tumors as seeds for vasculogenesis.Intercellular communication via gap junctions between neighboring cells contributes to the organization of cells into functional tissues. Malignant tumors arising from planar epithelial tissue lose the normal growth limit caused by cell-cell contacts and form solid tumors in three dimensions. This observation was the origin of the notion that the loss of gap junctional intercellular communication (GJIC) plays an important role in tumorigenesis [1,2]. Moreover, since invasive tumors are characterized by cell detachment from the primary mass, a disruption of intercellular junctions als
%U http://www.biomedcentral.com/1741-7015/6/20