Expression and function of beta 1 and alpha v beta 3 integrins in ovarian cancer.
Ovarian cancer cells disseminate by implanting onto the peritoneal mesothelial cell surface of the abdominal cavity. A common feature of these peritoneal implants is the presence of tumor cell invasion into the submesothelial extracellular matrix (ECM). In view of the important role of integrins in ECM recognition and cell migration, we were interested in defining the pattern of integrin expression and function in ovarian cancer cell lines and primary tissue samples. The beta 1 integrin chain was expressed by CAOV-3, SKOV-3, OVCAR-3, and SW626 ovarian cancer cell lines, associated with expression of alpha 1, -2, -3, -5, and -6 chains. The alpha 4 chain was also expressed by two of the four lines. In addition to beta 1 integrins, the alpha v beta 3 integrin was also expressed, although there was no expression of beta 2, -4, and -7 chains. Immunoprecipitation of surface-labeled CAOV-3 cells with an anti-beta 1 antibody revealed a band at approximately 110-130 kDa consistent with the known molecular mass of the beta 1 chain, as well as several associated bands consistent with noncovalently linked integrin alpha chains. A similar pattern of beta 1 and alpha v beta 3 integrin expression was observed for primary ovarian cancer tissue samples. Ovarian cancer cell lines exhibited significant binding to collagen type I and laminin which was primarily mediated by beta 1 integrins. In contrast, ovarian cancer cell binding to fibronectin was mediated by both alpha 5 beta 1 and alpha v beta 3 integrins. Even though mesothelial cells were observed to express fibronectin mRNA and protein, binding of ovarian cancer cells to peritoneal mesothelium was not blocked by neutralizing antibodies to beta 1 or alpha v beta 3 integrins. These data suggest that functional integrins are commonly expressed by ovarian cancer cells, although they do not appear to mediate ovarian cancer cell implantation onto peritoneal mesothelium. The role that integrins play in the invasion of ovarian cancer cells into the submesothelial ECM deserves further investigation.
Cannistra
S A
SA
Division of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Ottensmeier
C
C
Niloff
J
J
Orta
B
B
DiCarlo
J
J
D000595:Amino Acid Sequence; D002448:Cell Adhesion / Q000502:physiology; D003094:Collagen / Q000378:metabolism; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D019012:Integrin beta1; D016023:Integrins / Q000502:physiology*; D007797:Laminin / Q000378:metabolism; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology*; D010529:Peritoneal Cavity / Q000166:cytology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016024:Receptors, Cytoadhesin / Q000502:physiology*; D017469:Receptors, Fibronectin; D019030:Receptors, Vitronectin; D014407:Tumor Cells, Cultured
D005353:Fibronectins; D019012:Integrin beta1; D016023:Integrins; D007797:Laminin; D009842:Oligopeptides; D012333:RNA, Messenger; D016024:Receptors, Cytoadhesin; D017469:Receptors, Fibronectin; D019030:Receptors, Vitronectin; C047981:arginyl-glycyl-aspartic acid; D003094:Collagen