A 50 kDa protein present in conditioned medium of COLO-16 cells stimulates cell spreading and motility, and activates tyrosine phosphorylation of Neu/HER-2, in human SK-BR-3 mammary cancer cells.
A factor present in conditioned medium of COLO-16 human cancer cells causes fast spreading, fast plasma membrane ruffling, cell shape change, net translocation, stimulation of chemotaxis and growth arrest in human SK-BR-3 mammary cancer cells. Based on the spreading effect, the factor was purified to homogeneity and migrated as a 50 kDa protein in SDS-polyacrylamide gel electrophoresis. Addition of the purified 50 kDa factor to the target cells in culture results in tyrosine phosphorylation of the p185erbB2 receptor concomitant with a fast redistribution and clustering of the receptor. The 50 kDa factor is also specifically retained by affinity chromatography on the immobilized extracellular domain of p185erbB2. Antibodies directed against this domain also inhibit the induction of motility. These data suggest that the 50 kDa factor is a putative ligand of p185erbB2 in SK-BR-3 cells. Biochemical and immunological evidence further indicate that this factor differs from p185erbB2 ligands described so far. Its activity could play a role in the pathogenesis of breast cancer.
De Corte
V
V
Laboratory of Physiological Chemistry, University of Ghent, Belgium.
De Potter
C
C
Vandenberghe
D
D
Van Laerebeke
N
N
Azam
M
M
Roels
H
H
Mareel
M
M
Vandekerckhove
J
J
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001483:Base Sequence; D002455:Cell Division; D002460:Cell Line; D002465:Cell Movement; D017077:Culture Media, Conditioned; D004247:DNA; D066246:ErbB Receptors / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D015674:Mammary Neoplasms, Animal / Q000378:metabolism; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism*
D000906:Antibodies; D017077:Culture Media, Conditioned; D004247:DNA; D066246:ErbB Receptors; D008024:Ligands; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D014443:Tyrosine