Tumor cells express FcgammaRI which contributes to tumor cell growth and a metastatic phenotype.
High levels of circulating immune complexes containing tumor-associated antigens are associated with a poor prognosis for individuals with cancer. The ability of B cells, previously exposed to tumor-associated antigens, to promote both in vitro and in vivo tumor growth formed the rationale to evaluate the mechanism by which immune complexes may promote tumor growth. In elucidating this mechanism, FcgammaRI expression by tumor cells was characterized by flow cytometry, polymerase chain reaction, and sequence analysis. Immune complexes containing shed tumor antigen and anti-shed tumor antigen Ab cross-linked FcgammaRI-expressing tumor cells, which resulted in an induction of tumor cell proliferation and of shed tumor antigen production. Use of selective tyrosine kinase inhibitors demonstrated that tumor cell proliferation induced by immune complex cross-linking of FcgammaRI is dependent on the tyrosine kinase signal transduction pathway. A selective inhibitor of phosphatidylinositol-3 kinase also inhibited this induction of tumor cell proliferation. These findings support a role for immune complexes and FcgammaRI expression by tumor cells in augmentation of tumor growth and a metastatic phenotype.
Nelson
M B
MB
BioCrystal Ltd., Westerville, OH 43082-8888, USA.
Nyhus
J K
JK
Oravecz-Wilson
K I
KI
Barbera-Guillem
E
E
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism*; D002455:Cell Division; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D008954:Models, Biological; D009077:Mucins / Q000378:metabolism; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017452:Receptors, IgG / Q000096:biosynthesis* / Q000737:chemistry*; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D000911:Antibodies, Monoclonal; D004791:Enzyme Inhibitors; D009077:Mucins; D017452:Receptors, IgG; D014443:Tyrosine; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases