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

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

SN - 1476-5586

VL - 14

SP - 1260

EP - 1268

JO - Neoplasia (New York, N.Y.)

JF - Neoplasia (New York, N.Y.)

IS - 12

ER -