Anti-S100A4 antibody suppresses metastasis formation by blocking stroma cell invasion
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Anti-S100A4 antibody suppresses metastasis formation by blocking stroma cell invasion. / Klingelhöfer, Jörg; Grum-Schwensen, Birgitte; Beck, Mette K; Knudsen, Rikke Stagaard Petersen; Grigorian, Mariam; Lukanidin, Eugene; Ambartsumian, Noona.
In: Neoplasia (New York, N.Y.), Vol. 14, No. 12, 12.2012, p. 1260-1268.Research output: Contribution to journal › Journal article › peer-review
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TY - JOUR
T1 - Anti-S100A4 antibody suppresses metastasis formation by blocking stroma cell invasion
AU - Klingelhöfer, Jörg
AU - Grum-Schwensen, Birgitte
AU - Beck, Mette K
AU - Knudsen, Rikke Stagaard Petersen
AU - Grigorian, Mariam
AU - Lukanidin, Eugene
AU - Ambartsumian, Noona
PY - 2012/12
Y1 - 2012/12
N2 - 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.
AB - 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.
KW - Adenocarcinoma
KW - Animals
KW - Antibodies, Monoclonal
KW - Antibodies, Neoplasm
KW - Breast Neoplasms
KW - Cell Line, Tumor
KW - Cell Movement
KW - Epitope Mapping
KW - Fibroblasts
KW - Humans
KW - Lung Neoplasms
KW - Mice
KW - S100 Proteins
KW - Stromal Cells
KW - T-Lymphocytes
KW - Tumor Microenvironment
U2 - 10.1593/neo.121554
DO - 10.1593/neo.121554
M3 - Journal article
C2 - 23308057
VL - 14
SP - 1260
EP - 1268
JO - Neoplasia
JF - Neoplasia
SN - 1522-8002
IS - 12
ER -
ID: 48063178