Under the physiological shear condition, cultured colon cancer cells bound
to laminin (LM), but not to fibronectin or vitronectin. Most of the tethere
d cells did not roll, but arrested immediately and spread within 10-30 min
on LM under the continuous presence of shear flow. The tethering of Colo201
was partially inhibited by monoclonal antibodies (mAbs) to alpha 6 integri
n and a combination of mAbs to beta 1 and beta 4 integrins, but not by mAb
to 67KD laminin receptor. Some Colo201 cells still tethered at 4 degrees C.
This suggests that alpha 6 beta 1 and alpha 6 beta 4 integrins participate
in Colo201 tethering on LM, although other non-integrin molecules play rol
es. In contrast, the spread of Colo201 was effectively inhibited by the mAb
s to integrin alpha 2, alpha 6 and beta 1 chains. The effect of anti-alpha
2 plus anti-alpha 6 mAbs was almost equal to anti-beta 1, suggesting that C
olo201 cells mainly use alpha 2 beta 1 and alpha 6 beta 1 integrins for spr
eading on LM. When the cells were perfused on subconfluent endothelial cell
s (HUVEC) cultured on LM, they did not tether on HUVEC but did on coated LM
exposed at intercellular gap area. Immunohistochemistry revealed that LM a
bundantly existed in the cytosol of human portal and hepatic vein endotheli
al cells. These data suggest that LM can mediate from tethering to spreadin
g of colon cancer cells under the blood flow and plays an essential role in
haematogeneous metastasis.