THE INTEGRIN ALPHA(6)BETA(4) ON TA3 HA MAMMARY-CARCINOMA CELLS IS INVOLVED IN ADHESION TO HEPATOCYTES/

TA3/Ha mammary carcinoma cells form liver metastases upon intraportal injection. We have studied the interaction between these cells and hep atocytes that is likely to be important for liver metastasis formation . We show that the integrin alpha6beta4, which is highly expressed on TA3 cells, is involved in this interaction. Fab fragments, generated f rom a polyclonal serum against TA3 cells, inhibited TA3-hepatocyte adh esion. By affinity purification on purified alpha6beta4, we isolated a lpha6beta4-Specific Fab fragments from this anti-TA3 serum. These anti bodies were highly specific for alpha6beta4, as demonstrated by Wester n blot analysis and immunoprecipitation, and inhibited TA3-hepatocyte adhesion. This shows that alpha6beta4, which thus far has only been im plicated in cell-matrix adhesion, can also mediate interactions with c ell surfaces. Our results suggest that the high levels of alpha6beta4 often expressed by metastatic carcinoma cells contribute to liver meta stasis formation.