title: S100A4 expression in xenograft tumors of human carcinoma cell lines is induced by the tumor microenvironment.
abstract: Increased expression of the invasion- and metastasis-associated protein S100A4 is found in many types of cancer, but the regulation of S100A4 expression is poorly understood. The microenvironment surrounding tumors has a significant effect on tumor progression, and in the present study, we investigated the role of the microenvironment in the expression of S100A4. Tumors of three different human carcinoma cell lines were established in the tongue or skin of mice, and S100A4 expression was assessed by quantitative RT-PCR, Western blotting, and immunohistochemical analysis in tumors and stromal tissue and in cancer cells grown in vitro. Tongue tumors of the oral squamous cell carcinoma cell line HSC-4 showed a pronounced increase in S100A4 expression during tumor growth, whereas only a minor increase was detected in skin tumors of the same cell line. The S100A4 expression correlated with the methylation status of cytosine-guanine sites in the first intron of the gene. For all cell lines, S100A4 expression in the tumor stroma was related to the presence of inflammatory cells rather than to the level of S100A4 in the tumor cells.
authors.affiliation: Department of Pharmacy, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.
authors.forename: Hilde Ljones
authors.initials: HL
authors.lastname: Wetting
authors.forename: Elin
authors.initials: E
authors.lastname: Hadler-Olsen
authors.forename: Synnøve
authors.initials: S
authors.lastname: Magnussen
authors.forename: Oddveig
authors.initials: O
authors.lastname: Rikardsen
authors.forename: Sonja E
authors.initials: SE
authors.lastname: Steigen
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Sundkvist
authors.forename: Thrina
authors.initials: T
authors.lastname: Loennechen
authors.forename: Premasany
authors.initials: P
authors.lastname: Kanapathippillai
authors.forename: Hanne
authors.initials: H
authors.lastname: Kildalsen
authors.forename: Jan-Olof
authors.initials: JO
authors.lastname: Winberg
authors.forename: Lars
authors.initials: L
authors.lastname: Uhlin-Hansen
authors.forename: Gunbjørg
authors.initials: G
authors.lastname: Svineng
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000096:biosynthesis*; D014183:Transplantation, Heterologous; D059016:Tumor Microenvironment
chemical_list: D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C077591:S100A4 protein, human