IgG-recognizing shed tumor-associated antigens can promote tumor invasion and metastasis

Tumors secreting glycoproteins that act as tumor-associated antigens have b een described as highly invasive and metastatic. In this study, the consequ ences of the humoral immune response (HIR) against these antigens were inve stigated. Using an in vitro model of tumor cell invasion, results indicated that the invasiveness of tumor cells secreting antigenic secreted/shed tum or glycoproteins (STGP) increases in the presence of specific anti-STGP IgG , polymorphonuclear cells and monocytes. This in vitro model showed that th e coincidental presence in the matrix of both STGP and specific anti-STGP I gG increases the local release of IL-1 beta, IL-6 and vascular endothelial growth factor (VEGF) by stromal cells, but not by tumor cells. Using an in vivo model, the experiments show that immune-competent mice develop an anti -tumor HIR with anti-STGP IgG production. In this model, tumor growth was i ncreased in parallel with the serum concentration of specific anti-STGP IgG . In athymic nude (nu/nu)-beige mice the same trend was observed, suggestin g a T-cell-independent tumor-promoting effect induced by anti-STGP I-G. Tum or histology showed intense infiltration of IgG-positive plasma cells and l ymphocytes. A severe combined immunodeficient-beige mouse-based in vivo mod el of tumors, experimentally infiltrated with monoclonal IgG plasmocytoma c ells, showed that only specific anti-STGP-IgG-secreting cells could exacerb ate tumor invasion, angiogenesis and metastasis. These results suggest that tumors shedding/secreting antigenic STGP can induce a host IgG immune resp onse that can promote invasion and metastasis by inducing tumor infiltratin g stromal cells to release proinflammatory cytokines and VEGF.