title: Anti-S100A4 antibody suppresses metastasis formation by blocking stroma cell invasion.
abstract: The small Ca-binding protein, S100A4, has a well-established metastasis-promoting activity. Moreover, its expression is tightly correlated with poor prognosis in patients with numerous types of cancer. Mechanistically, the extracellular S100A4 drives metastasis by affecting the tumor microenvironment, making it an attractive target for anti-cancer therapy. In this study, we produced a function-blocking anti-S100A4 monoclonal antibody with metastasis-suppressing activity. Antibody treatment significantly reduced metastatic burden in the lungs of experimental animals by blocking the recruitment of T cells to the site of the primary tumor. In vitro studies demonstrated that this antibody efficiently reduced the invasion of T cells in a fibroblast monolayer. Moreover, it was capable of suppressing the invasive growth of human and mouse fibroblasts. We presume therefore that the antibody exerts its activity by suppressing stroma cell recruitment to the site of the growing tumor. Our epitope mapping studies suggested that the antibody recognition site overlaps with the target binding interface of human S100A4. We conclude here that this antibody could serve as a solid basis for development of an efficient anti-metastatic therapy.
authors: Department of Tumor Microenvironment and Metastasis, Danish Cancer Society, Copenhagen Ø, Denmark. klingelhofer@sund.ku.dk
authors: Jörg
authors: J
authors: Klingelhöfer
authors: Birgitte
authors: B
authors: Grum-Schwensen
authors: Mette K
authors: MK
authors: Beck
authors: Rikke Stagaard Petersen
authors: RS
authors: Knudsen
authors: Mariam
authors: M
authors: Grigorian
authors: Eugene
authors: E
authors: Lukanidin
authors: Noona
authors: N
authors: Ambartsumian
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology* / Q000556:secondary; D000818:Animals; D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D018604:Epitope Mapping; D005347:Fibroblasts; D006801:Humans; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary*; D051379:Mice; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000276:immunology*; D017154:Stromal Cells; D013601:T-Lymphocytes / Q000276:immunology; D059016:Tumor Microenvironment / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C470944:S100a4 protein, mouse; C077591:S100A4 protein, human