Biomaterial Database

Cell-cell interactions during transendothelial migration of tumor cells. 1998

E B Voura, and M Sandig, and C H Siu

Banting and Best Department of Medical Research, University of Toronto, Ontario, Canada.

A key event in cancer metastasis is the transendothelial migration of tumor cells. This process involves multiple adhesive interactions between tumor cells and the endothelium. After adhering to the surface of endothelial cells, tumor cells must penetrate the endothelial junction, which contains high concentrations of the cell adhesion molecules VE-cadherin and PECAM-1. Studies using an in vitro model system, consisting of melanoma cells which are seeded onto a monolayer of endothelial cells cultured on Matrigel, have revealed reorganization of the cytoskeleton and dynamic changes in the cell shape of both tumor and endothelial cells. The initial stages of transmigration are characterized by numerous membrane blebs protruding from the basolateral surfaces of the melanoma cells. Contact regions also show an abundance of microfilaments arising from the underlying endothelial cells. These adhesive interactions lead to the redistribution of both VE-cadherin and PECAM-1 and, consequently, a localized dissolution of the endothelial junction. The penetration of the endothelial junction is initiated by melanoma pseudopods. Despite the disappearance of VE-cadherin from the retracting endothelial junction, heterotypic contacts between the tumor cell and its surrounding endothelial cells show a high concentration of pan-cadherin staining, suggesting that transmigration of melanoma cells might yet be facilitated by interactions with another member of the cadherin family. Upon adhesion to the Matrigel, melanoma cells begin to spread and invade the matrix material, while the endothelial cells extend processes over the melanoma cells to reform the monolayer. Interestingly, the leading margins of these endothelial processes contain a high concentration ofN-cadherin. VE-cadherin and PECAM-1 reappear only when the advancing endothelial processes meet to reform the endothelial junction. Together, these observations suggest that endothelial cells actively participate in the transmigration of tumor cells and specific cadherins are involved in different steps of this complex process.

UI	MeSH Term	Description	Entries
D008545	Melanoma	A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445)	Malignant Melanoma,Malignant Melanomas,Melanoma, Malignant,Melanomas,Melanomas, Malignant
D002450	Cell Communication	Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP.	Cell Interaction,Cell-to-Cell Interaction,Cell Communications,Cell Interactions,Cell to Cell Interaction,Cell-to-Cell Interactions,Communication, Cell,Communications, Cell,Interaction, Cell,Interaction, Cell-to-Cell,Interactions, Cell,Interactions, Cell-to-Cell
D002465	Cell Movement	The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.	Cell Migration,Locomotion, Cell,Migration, Cell,Motility, Cell,Movement, Cell,Cell Locomotion,Cell Motility,Cell Movements,Movements, Cell
D004730	Endothelium, Vascular	Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.	Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D014407	Tumor Cells, Cultured	Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.	Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D015815	Cell Adhesion Molecules	Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis.	Cell Adhesion Molecule,Intercellular Adhesion Molecule,Intercellular Adhesion Molecules,Leukocyte Adhesion Molecule,Leukocyte Adhesion Molecules,Saccharide-Mediated Cell Adhesion Molecules,Saccharide Mediated Cell Adhesion Molecules,Adhesion Molecule, Cell,Adhesion Molecule, Intercellular,Adhesion Molecule, Leukocyte,Adhesion Molecules, Cell,Adhesion Molecules, Intercellular,Adhesion Molecules, Leukocyte,Molecule, Cell Adhesion,Molecule, Intercellular Adhesion,Molecule, Leukocyte Adhesion,Molecules, Cell Adhesion,Molecules, Intercellular Adhesion,Molecules, Leukocyte Adhesion
D015820	Cadherins	Calcium-dependent cell adhesion proteins. They are important in the formation of ADHERENS JUNCTIONS between cells. Cadherins are classified by their distinct immunological and tissue specificities, either by letters (E- for epithelial, N- for neural, and P- for placental cadherins) or by numbers (cadherin-12 or N-cadherin 2 for brain-cadherin). Cadherins promote cell adhesion via a homophilic mechanism as in the construction of tissues and of the whole animal body.	Cadherin,E-Cadherins,Epithelial-Cadherin,Liver Cell Adhesion Molecules,N-Cadherins,Neural Cadherin,P-Cadherins,Uvomorulin,Cadherin-1,Cadherin-2,Cadherin-3,E-Cadherin,Epithelial-Cadherins,Liver Cell Adhesion Molecule,N-Cadherin,Neural Cadherins,P-Cadherin,Placental Cadherins,Cadherin 1,Cadherin 2,Cadherin 3,Cadherin, Neural,Cadherins, Neural,Cadherins, Placental,E Cadherin,E Cadherins,Epithelial Cadherin,Epithelial Cadherins,N Cadherin,N Cadherins,P Cadherin,P Cadherins
D018613	Microscopy, Confocal	A light microscopic technique in which only a small spot is illuminated and observed at a time. An image is constructed through point-by-point scanning of the field in this manner. Light sources may be conventional or laser, and fluorescence or transmitted observations are possible.	Confocal Microscopy,Confocal Microscopy, Scanning Laser,Laser Microscopy,Laser Scanning Confocal Microscopy,Laser Scanning Microscopy,Microscopy, Confocal, Laser Scanning,Confocal Laser Scanning Microscopy,Confocal Microscopies,Laser Microscopies,Laser Scanning Microscopies,Microscopies, Confocal,Microscopies, Laser,Microscopies, Laser Scanning,Microscopy, Laser,Microscopy, Laser Scanning,Scanning Microscopies, Laser,Scanning Microscopy, Laser