Effect of the hepatitis B virus HBx protein on integrin-mediated adhesion to and migration on extracellular matrix.
OBJECTIVE
The hepatitis B virus HBx protein is associated with the development of hepatocellular carcinoma (HCC). However, its possible contribution to tumor spreading has not been explored. The migration of tumor cells through the extracellular matrix (ECM) represents a crucial step in tumor metastasis. Our aim was to study the effect of HBx on the integrin-mediated cell-ECM interaction, and its possible consequences for cell migration.


METHODS
Cell-ECM interaction was evaluated by static adhesion experiments, using blocking and stimulating anti-beta1 integrin mAbs. ECM receptor expression was analyzed by flow cytometry. The cellular distribution of the activated beta1 integrin subunit was determined by immunofluorescence analysis, and cell motility was determined by wound-healing assays.


RESULTS
HBx-bearing cells showed decreased adhesion to fibronectin, which correlated with a decreased expression of the alpha5 integrin subunit. The activated beta1 subunit was redistributed to the tips of pseudopodial protrusions of HBx-bearing cells, whereas it was evenly localized in the control cells. HBx-induced cell migration was abrogated by irreversible stimulation of beta1 integrins.


CONCLUSIONS
These results suggest that HBx might play a role in tumor spreading by modulating the adhesion-deadhesion balance of the cells in the primary tumor site and favoring integrin-mediated cell migration.
Lara-Pezzi
E
E
Unidad de Biología Molecular, Hospital Universitario de la Princesa, Madrid, Spain.
Majano
P L
PL
Yáñez-Mó
M
M
Gómez-Gonzalo
M
M
Carretero
M
M
Moreno-Otero
R
R
Sánchez-Madrid
F
F
López-Cabrera
M
M
D015703:Antigens, CD / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology*; D005353:Fibronectins / Q000502:physiology; D039423:Integrin alpha1; D039482:Integrin alpha5; D019012:Integrin beta1 / Q000502:physiology; D016023:Integrins / Q000502:physiology*; D015534:Trans-Activators / Q000494:pharmacology*; D014162:Transfection; D054334:Viral Regulatory and Accessory Proteins
D015703:Antigens, CD; D005353:Fibronectins; D039423:Integrin alpha1; D039482:Integrin alpha5; D019012:Integrin beta1; D016023:Integrins; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein