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Expression of S100A4 by a variety of cell types present in the tumor microenvironment of human breast cancer
Author(s) -
Cabezón Teresa,
Celis Julio E.,
Skibshøj Inge,
Klingelhöfer Jörg,
Grigorian Mariam,
Gromov Pavel,
Rank Fritz,
Myklebust June Helen,
Mælandsmo Gunhild M.,
Lukanidin Eugene,
Ambartsumian Noona
Publication year - 2007
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22850
Subject(s) - tumor microenvironment , immunohistochemistry , stroma , breast cancer , biology , metastasis , pathology , cancer , cancer research , cell type , cancer cell , cell , antibody , medicine , immunology , tumor cells , genetics
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). © 2007 Wiley‐Liss, Inc.