Expression of S100A4 by a variety of cell types present in the tumor microenvironment of human breast cancer

TY - JOUR

T1 - Expression of S100A4 by a variety of cell types present in the tumor microenvironment of human breast cancer

AU - Cabezón, Teresa

AU - Celis, Julio E

AU - Skibshøj, Inge

AU - Klingelhöfer, Jörg

AU - Grigorian, Mariam

AU - Gromov, Pavel

AU - Rank, Fritz

AU - Myklebust, June Helen

AU - Maelandsmo, Gunhild M

AU - Lukanidin, Eugene

AU - Ambartsumian, Noona

PY - 2007/10/1

Y1 - 2007/10/1

N2 - The S100A4 protein, which is involved in the metastasis process, is a member of the S100 superfamily of Ca-binding proteins. Members of this family are multifunctional signaling proteins with dual extra and intracellular functions involved in the regulation of diverse cellular processes. Several studies have established a correlation between S100A4 protein expression and worse prognosis for patients with various malignancies including breast cancer. In this article, we have used specific antibodies in combination with immunohistochemistry (IHC) to identify the cell types that express S100A4 in human breast cancer biopsies obtained from high-risk patients. IHC analysis of 68 tumor biopsies showed that the protein is expressed preferentially by various cell types present in the tumor microenvironment (macrophages, fibroblasts, activated lymphocytes), rather than by the tumor cells themselves. Moreover, we show that the protein is externalized by the stroma cells to the fluid that bathes the tumor microenvironment, where it is found in several forms that most likely correspond to charge variants. Using a specific ELISA test, we detected a significant higher concentration of S100A4 in the tumor interstitial fluid (TIF) as compared to their corresponding normal counterparts (NIF).

AB - The S100A4 protein, which is involved in the metastasis process, is a member of the S100 superfamily of Ca-binding proteins. Members of this family are multifunctional signaling proteins with dual extra and intracellular functions involved in the regulation of diverse cellular processes. Several studies have established a correlation between S100A4 protein expression and worse prognosis for patients with various malignancies including breast cancer. In this article, we have used specific antibodies in combination with immunohistochemistry (IHC) to identify the cell types that express S100A4 in human breast cancer biopsies obtained from high-risk patients. IHC analysis of 68 tumor biopsies showed that the protein is expressed preferentially by various cell types present in the tumor microenvironment (macrophages, fibroblasts, activated lymphocytes), rather than by the tumor cells themselves. Moreover, we show that the protein is externalized by the stroma cells to the fluid that bathes the tumor microenvironment, where it is found in several forms that most likely correspond to charge variants. Using a specific ELISA test, we detected a significant higher concentration of S100A4 in the tumor interstitial fluid (TIF) as compared to their corresponding normal counterparts (NIF).

KW - Adult

KW - Aged, 80 and over

KW - Antibodies, Monoclonal

KW - Antibody Specificity

KW - Blotting, Western

KW - Breast Neoplasms

KW - Electrophoresis, Gel, Two-Dimensional

KW - Enzyme-Linked Immunosorbent Assay

KW - Female

KW - Fibroblasts

KW - Humans

KW - Immunohistochemistry

KW - Lymphocytes

KW - Macrophages

KW - Middle Aged

KW - S100 Proteins

U2 - 10.1002/ijc.22850

DO - 10.1002/ijc.22850

M3 - Journal article

C2 - 17565747

SN - 0020-7136

VL - 121

SP - 1433

EP - 1444

JO - Radiation Oncology Investigations

JF - Radiation Oncology Investigations

IS - 7

ER -