Adhesion-mediated gap junctional communication between lung-metastatatic cancer cells and endothelium.
Invasion Metastasis
; 14(1-6): 164-76, 1994.
Article
en En
| MEDLINE
| ID: mdl-7657509
ABSTRACT
Adhesion to vascular endothelium is a primary step in the colonization of select target organs by blood-borne cancer cells. Previous studies in our laboratory have shown that adhesion is followed by the establishment of fully functional gap junctional channels between the arrested tumor cell and the endothelium and that gap junctional communication might play an important role in extravasation. Here we report on a critical interdependence between endothelial cell adhesion and communication of lung-metastatic cancer cells. Gap junctions are assembled at focal adhesion contacts between tumor cells and endothelial cells where they mediate metabolic coupling between the junction-forming cell pair. The level of coupling depends on sufficient amounts of connexin43 (cx43) protein expression by both cell partners and, in a rate-limiting fashion, on the expression level of the receptor/ligand pair that mediates adhesion between tumor cells and the endothelium. This conclusion is based on our findings that (a) tumor cells with equal cx43 message, yet different adhesion potential for endothelial cells, differ significantly in their level of communication with the endothelium (e.g., R230AC-MET vs. R3230AC-LR), and (b) gap junctional communication between B16-F10 melanoma cells and lung-matrix-modulated endothelium can be effectively blocked by antiadhesive, anti-Lu-ECAM-1 monoclonal antibody 6D3 and by soluble Lu-ECAM-1. Significantly increased adhesion and communication levels in highly lung-metastatic carcinoma cells imply a role of gap junctional coupling in cancer metastasis, presumably by facilitating extravasation.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Melanoma Experimental
/
Endotelio Vascular
/
Uniones Comunicantes
/
Neoplasias Pulmonares
Límite:
Animals
Idioma:
En
Revista:
Invasion Metastasis
Año:
1994
Tipo del documento:
Article
País de afiliación:
Estados Unidos