Complement-mediated killing of microtumors in vitro.
Complement-mediated lysis of cancer cells growing in three-dimensional aggregates involves factors that are not associated with the killing of cells in suspension. We have used multicellular tumor spheroids established from breast carcinoma (T47D) and ovarian teratocarcinoma (PA-1) cell lines as models to study complement-mediated destruction of micrometastases and small solid tumors. We found that significant killing of microtumors treated with an antitumor antibody and a specific monoclonal antibody (YTH53.1) against the complement lysis inhibitor protectin (CD59) started to occur after a 1 to 2-hour lag phase. After an overnight incubation, the microtumors became totally infiltrated by the YTH53.1 monoclonal antibody and C1q, whereas C3 and C5b-9 penetrated as a frontier to the peripheral cell layers. A 51Cr release assay showed that during a 24-hour pulsed treatment with complement, 33% of cells in the spheroids were killed, and the average tumor volume decreased by 28%. According to propidium iodide staining, complement exposure resulted in killing and peeling off of the outermost tumor cells.
Hakulinen
J
J
Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Finland.
Meri
S
S
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000912:Antibodies, Neoplasm / Q000494:pharmacology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology*; D018957:CD59 Antigens / Q000276:immunology; D018270:Carcinoma, Ductal, Breast / Q000276:immunology / Q000473:pathology*; D016923:Cell Death / Q000187:drug effects; D003167:Complement Activation; D003165:Complement System Proteins / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D010051:Ovarian Neoplasms / Q000276:immunology / Q000473:pathology*; D018874:Spheroids, Cellular / Q000276:immunology / Q000473:pathology; D018243:Teratocarcinoma / Q000276:immunology / Q000473:pathology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D018957:CD59 Antigens; D003165:Complement System Proteins