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Figure 10 | BMC Medicine

Figure 10

From: Connexin-43 upregulation in micrometastases and tumor vasculature and its role in tumor cell attachment to pulmonary endothelium

Figure 10

Apical endothelial cell connexin 43 forms heterologous gap junctions. (A) Connexin-43 (Cx43) localization at the interface between the endothelial apical surface and the 4T1-GFP cell coupling surface. The picture shows a side view of a 4T1-GFP cell sitting on top of an endothelial cell in culture. The side view was generated from a three-dimensional reconstructed image from a stack of 20 z-axis optical sections of the cells. (B) Model of cancer cell attachment to endothelial cells. The gap junctional coupling mediated via Cx43 would require its localization on the surfaces in contact: the apical surface of the endothelial cells and the coupling surface of the cancer cell. Our results suggest that the initial attachment mediated via the classical cell adhesion molecules (such as α3β1 integrin and vascular laminin-5 [42]) may not be sufficient for retention of the cells and the creation of metastatic foci. This requires establishment of functional gap junctions between the apposing surfaces brought together by cell adhesion molecules. In our model, the required molecule playing an important role in the adhesion efficiency is Cx43, as demonstrated by the loss of adhesion with gap junctional intercellular communication incompetent G138R mutant variant in the cancer cell alone. How the communication helps the establishment of the metastatic foci is unknown at present, but we speculate that the coordination between the disparate cell types helps them to recognize each other as partners and makes them grow together to become a tumor mass with blood supply.

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