In an adhesion dependent human gastric adenocarcinoma cell line, integrin ligation without adhesion rescues from anoikis but is not sufficient for cell cycle progression

STAD cells are the adherent parental apoptotic line from which two sublines were cloned that differed in their response to suspended culturing conditions, one clone STAD.APO is apoptotic and the other STAD.ARR goes into cell cycle arrest. Using this system we have found that the addition of soluble collagen can rescue STAD and STAD.APO cells from anoikis, and it can also affect STAD.ARR cells by overcoming the suspension induced cell cycle arrest. In contrast, when cells were cultured with a soluble anti-β1 integrin mAb 33B6, the apoptotic clones again were rescued from anoikis, but the cell cycle arresting clone remained quiescent. This result was somewhat surprising as it is generally accepted that cytoskeletal rearrangements that accompany integrin mediated adhesion and cell shape changes are required for the abrogation of anoikis, and it was unexpected that differences in the mechanism used for integrin triggering would yield variable results on growth regulation. This observation led us to further examine whether the addition of a monovalent anti-β1 integrin agent could produce similar results as intact mAb. Therefore we employed Fab fragments of 33B6 in our culturing assay and found that indeed monovalent binding was capable of saving STAD and STAD.APO cells from anoikis but did not have an effect on STAD.ARR cells. Therefore in this study we have observed that integrin mediated dependent survival can occur by mere ligation of the β1 integrin subunit, but that cell cycle arrest due to suspended conditions can not. Thus integrins can play differential roles in cell fate decisions and mediate these effects by different mechanisms. Cell Death and Differentiation (2001) 8, 665–678