Anti-beta4 integrin antibodies enhance migratory and invasive abilities of human colon adenocarcinoma cells and their MMP-2 expression.
Integrin-mediated adhesion of cells to extracellular matrix proteins has been shown to activate various intracellular signaling events. In the present study, we demonstrate that the addition of a monoclonal antibody raised against the beta4 integrin subunit in the culture medium of a clone derived from the colon adenocarcinoma cell line LoVo specifically results in stimulation of cell migration and invasion through reconstituted basement membrane matrices. Moreover, an increase in MMP-2 activity is observed. Conversely, monoclonal anti-alpha6 and anti-beta1 have no effect on MMP-2 expression. The s. c. co-injection of adenocarcinoma cells with antibodies raised against the beta4 integrin subunit to immunosuppressed newborn rats gives rise to tumors displaying altered and disorganized peri-tumoral basement membranes compared with tumors obtained when cells are injected with adenocarcinoma cells alone. Higher metastatic capacity of cells results when they are co-injected with antibodies to the beta4 integrin subunit. Our results suggest that the beta4 subunit of alpha6beta4 integrin, a laminin receptor in colon adenocarcinoma, may be responsible for the specific signals which stimulate cell motility, expression of MMP-2 and tumor invasion.
Daemi
N
N
INSERM U 45, Hôpital Edouard Herriot, Lyon, France.
Thomasset
N
N
Lissitzky
J C
JC
Dumortier
J
J
Jacquier
M F
MF
Pourreyron
C
C
Rousselle
P
P
Chayvialle
J A
JA
Remy
L
L
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D015139:Blotting, Southern; D002465:Cell Movement; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D039663:Integrin beta4; D007797:Laminin / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008854:Microscopy, Electron; D009361:Neoplasm Invasiveness; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D039663:Integrin beta4; D007797:Laminin; C121346:laminin 1; D020778:Matrix Metalloproteinase 2