Head and neck squamous cancer stromal fibroblasts produce growth factors influencing phenotype of normal human keratinocytes.
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.
Strnad
Hynek
H
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Lacina
Lukás
L
Kolár
Michal
M
Cada
Zdenek
Z
Vlcek
Cestmír
C
Dvoránková
Barbora
B
Betka
Jan
J
Plzák
Jan
J
Chovanec
Martin
M
Sáchová
Jana
J
Valach
Jaroslav
J
Urbanová
Markéta
M
Smetana
Karel
K
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
D055415:Bone Morphogenetic Protein 4; D011994:Recombinant Proteins; D007335:Insulin-Like Growth Factor II