Expression of S100A4 by a variety of cell types present in the tumor microenvironment of human breast cancer.
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).
Cabezón
Teresa
T
Department of Proteomics in Cancer, Institute of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark.
Celis
Julio E
JE
Skibshøj
Inge
I
Klingelhöfer
Jörg
J
Grigorian
Mariam
M
Gromov
Pavel
P
Rank
Fritz
F
Myklebust
June Helen
JH
Maelandsmo
Gunhild M
GM
Lukanidin
Eugene
E
Ambartsumian
Noona
N
D000328:Adult; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005347:Fibroblasts / Q000737:chemistry / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008214:Lymphocytes / Q000737:chemistry / Q000473:pathology; D008264:Macrophages / Q000737:chemistry / Q000473:pathology; D008875:Middle Aged; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology
D000911:Antibodies, Monoclonal; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C077591:S100A4 protein, human