Anti-S100A4 antibody suppresses metastasis formation by blocking stroma cell invasion

Research output: Contribution to journalJournal articleResearchpeer-review

  • Jörg Klingelhöfer
  • Birgitte Grum-Schwensen
  • Lademann, Mette
  • Rikke Stagaard Petersen Knudsen
  • Mariam Grigorian
  • Eugene Lukanidin
  • Noona Ambartsumian
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.
Original languageEnglish
JournalNeoplasia (New York, N.Y.)
Volume14
Issue number12
Pages (from-to)1260-1268
Number of pages9
DOIs
Publication statusPublished - Dec 2012

    Research areas

  • Adenocarcinoma, Animals, Antibodies, Monoclonal, Antibodies, Neoplasm, Breast Neoplasms, Cell Line, Tumor, Cell Movement, Epitope Mapping, Fibroblasts, Humans, Lung Neoplasms, Mice, S100 Proteins, Stromal Cells, T-Lymphocytes, Tumor Microenvironment

ID: 48063178