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-beta1 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-beta1 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 beta1 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.
Caruso
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DA
Department of Immunology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
McIntyre
B W
BW
D000199:Actins / Q000378:metabolism; D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology*; D023102:Anoikis / Q000187:drug effects; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D002448:Cell Adhesion; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division; D048429:Cell Size; D003094:Collagen / Q000378:metabolism / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D015870:Gene Expression; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology / Q000494:pharmacology; D019012:Integrin beta1 / Q000276:immunology / Q000378:metabolism*; D016023:Integrins / Q000276:immunology / Q000378:metabolism*; D007700:Kinetics; D008856:Microscopy, Fluorescence; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*; D014407:Tumor Cells, Cultured
D000199:Actins; D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D019012:Integrin beta1; D016023:Integrins; D003094:Collagen; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human