Decreased adhesion to endothelial cells and matrix proteins of H-2Kb gene transfected tumour cells.
Transfection of murine metastatic B78H1 cells (derived from B16 melanoma) with a syngeneic H-2Kb gene was used to study the effect of Major Histocompatibility Complex (MHC) gene products on tumour cell adhesion to endothelial cells and matrix proteins and the involvement in the metastatic process. H-2Kb-expressing transfectants showed a reduced adhesion to endothelial surfaces of different origin (four murine endotheliomas and human umbilical vein endothelial cells) when compared to parental B78H1 cells and to controls transfected with pSV2neo alone. On the average a 50-70% reduction in adhesion to endothelial cells was observed among H-2Kb transfectants. H-2Kb transfectants had a reduced expression of the alpha 4 integrin subunit, moreover the adhesion of Neo-transfected clones to endothelial cells was reduced to the levels of H-2Kb transfectants by antibodies directed against the beta 1 subunit and the endothelial VCAM-1 molecule, thus suggesting an impairment of the VLA-4/VCAM-1 interaction in H-2Kb transfectants. Adhesion to extracellular matrix components was also strongly decreased: in general the adhesion of H-2Kb cells showed a 50-75% inhibition with respect to Neo or parental controls. The highest difference was observed in adhesion to vitronectin and laminin, the lowest in adhesion to fibronectin. Reduction in adhesive properties of H-2Kb-expressing transfectants could be involved in the reduced metastatic ability, evaluated by means of intravenous injection of cells: H-2Kb transfectants yielded less than ten lung colonies, while all controls produced more than 100. Our data indicate that expression of a single class I MHC gene can significantly alter the metastatic phenotype of MHC-negative tumour cells and this could be related to a general alteration of tumour cell adhesive interactions.
Lauri
D
D
Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
De Giovanni
C
C
Biondelli
T
T
Lalli
E
E
Landuzzi
L
L
Facchini
A
A
Nicoletti
G
G
Nanni
P
P
Dejana
E
E
Lollini
P L
PL
D000818:Animals; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology; D002460:Cell Line; D004730:Endothelium, Vascular / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D005805:Genes, MHC Class I; D006183:H-2 Antigens / Q000235:genetics*; D008546:Melanoma, Experimental / Q000473:pathology*; D051379:Mice; D009362:Neoplasm Metastasis; D014162:Transfection; D014407:Tumor Cells, Cultured; D019010:Vascular Cell Adhesion Molecule-1
D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D019010:Vascular Cell Adhesion Molecule-1