title: Head and neck squamous cancer stromal fibroblasts produce growth factors influencing phenotype of normal human keratinocytes.
abstract: Epithelial-mesenchymal interaction between stromal fibroblasts and cancer cells influences the functional properties of tumor epithelium, including the tumor progression and spread. We compared fibroblasts prepared from stroma of squamous cell carcinoma and normal dermal fibroblasts concerning their biological activity toward normal keratinocytes assessed by immunocytochemistry and profiling of gene activation for growth factors/cytokines by microarray chip technology. IGF-2 and BMP-4 were determined as candidate factors responsible for tumor-associated fibroblast activity that influences normal epithelia. This effect was confirmed by addition of recombinant IGF-2 and BMP4, respectively, to the culture medium. This hypothesis was also verified by inhibition experiments where blocking antibodies were employed in the medium conditioned by cancer-associated fibroblast. Presence of these growth factors was also detected in tumor samples.
authors.affiliation: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Hynek
authors.initials: H
authors.lastname: Strnad
authors.forename: Lukás
authors.initials: L
authors.lastname: Lacina
authors.forename: Michal
authors.initials: M
authors.lastname: Kolár
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Cada
authors.forename: Cestmír
authors.initials: C
authors.lastname: Vlcek
authors.forename: Barbora
authors.initials: B
authors.lastname: Dvoránková
authors.forename: Jan
authors.initials: J
authors.lastname: Betka
authors.forename: Jan
authors.initials: J
authors.lastname: Plzák
authors.forename: Martin
authors.initials: M
authors.lastname: Chovanec
authors.forename: Jana
authors.initials: J
authors.lastname: Sáchová
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Valach
authors.forename: Markéta
authors.initials: M
authors.lastname: Urbanová
authors.forename: Karel
authors.initials: K
authors.lastname: Smetana
mesh_terms: D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000096:biosynthesis*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis*; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D010641:Phenotype; D040081:Protein Array Analysis; D011994:Recombinant Proteins / Q000096:biosynthesis
chemical_list: D055415:Bone Morphogenetic Protein 4; D011994:Recombinant Proteins; D007335:Insulin-Like Growth Factor II