The Met receptor and alpha 6 beta 4 integrin can function independently to promote carcinoma invasion.
It has been proposed that a constitutive, physical association of the Met receptor and the alpha(6)beta(4) integrin exists on the surface of invasive carcinoma cells and that hepatocyte growth factor (HGF)-mediated invasion is dependent on alpha(6)beta(4) (Trusolino, L., Bertotti, A., and Comoglio, P. M. (2001) Cell 107, 643-654). The potential significance of these results prompted us to re-examine this hypothesis. Using three different carcinoma cell lines that express both Met and alpha(6)beta(4), we were unable to detect the constitutive association of these receptors by co-immunoprecipitation. Moreover, carcinoma cells that lacked expression of alpha(6)beta(4) exhibited Met-dependent invasion toward HGF, and increasing Met expression by viral infection of these cells enhanced invasion without inducing alpha(6)beta(4) expression. Although expression of alpha(6)beta(4) in such cells enhanced their invasion to HGF, it also enhanced their ability to invade toward other chemoattractants such as lysophosphatidic acid, and this latter invasion was not inhibited by a function-blocking Met antibody. Finally, depletion of beta(4) by RNA interference in invasive carcinoma cells that express both receptors reduced the ability of these cells to invade toward HGF by approximately 25%, but it did not abrogate their invasion. These data argue that the invasive function of Met can be independent of alpha(6)beta(4) and that alpha(6)beta(4) has a generic influence on the invasion of carcinoma cells that is not specific to Met.
Chung
Jun
J
Division of Cancer Biology and Angiogenesis, Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
Yoon
Sang-Oh
SO
Lipscomb
Elizabeth A
EA
Mercurio
Arthur M
AM
D016475:3T3 Cells; D000818:Animals; D002277:Carcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned / Q000494:pharmacology; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D039161:Integrin alpha6beta4 / Q000378:metabolism*; D039663:Integrin beta4 / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism; D051379:Mice; D009361:Neoplasm Invasiveness; D011233:Precipitin Tests; D011506:Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D019859:Proto-Oncogene Proteins c-met; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D017978:Receptors, Growth Factor; D012190:Retroviridae / Q000235:genetics; D013997:Time Factors
D017077:Culture Media, Conditioned; D039161:Integrin alpha6beta4; D039663:Integrin beta4; D008246:Lysophospholipids; D011506:Proteins; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D017978:Receptors, Growth Factor; D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; C032881:lysophosphatidic acid