The inhibition of tumor cell intravasation and subsequent metastasis via regulation of in vivo tumor cell motility by the tetraspanin CD151.
In vivo tumor cell migration through integrin-dependent pathways is key to the metastatic behavior of malignant cells. Using quantitative in vivo assays and intravital imaging, we assessed the impact of cell migration, regulated by the integrin-associated tetraspanin CD151, on spontaneous human tumor cell metastasis. We demonstrate that promoting immobility through a CD151-specific metastasis blocking mAb prevents tumor cell dissemination by inhibiting intravasation without affecting primary tumor growth, tumor cell arrest, extravasation, or growth at the secondary site. In vivo, this loss of migration is the result of enhanced tumor cell-matrix interactions, promoted by CD151, which prevent dissociation by individual cells and leads to a subsequent inhibition of invasion and intravasation at the site of the primary tumor.
Zijlstra
Andries
A
Department of Cell Biology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. andries.zijlstra@vanderbilt.edu
Lewis
John
J
Degryse
Bernard
B
Stuhlmann
Heidi
H
Quigley
James P
JP
D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001666:Binding Sites, Antibody; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D060185:Tetraspanin 24; D013997:Time Factors; D014162:Transfection
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C554715:CD151 protein, human; C554716:Cd151 protein, mouse; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D060185:Tetraspanin 24