The production of the endostatin precursor collagen XVIII in head and neck carcinomas is modulated by CBP2/Hsp47.
Tumor progression is dependent in large part on angiogenesis and angiogenesis inhibitors have repeatedly been shown to inhibit tumor growth. The present study sought to determine whether the oral squamous carcinoma cells expressed and produced collagen XVIII, a known precursor of endostatin. Four established cell lines of oral squamous cell carcinoma (SCC) were employed for these studies. Quantitative Real-Time RT-PCR was used to assess the expression of collagen XVIII and CBP2/Hsp47, an ostensible chaperone for fibrillar and basement membrane collagens. Real-Time PCR assessment of collagen XVIII with primers selected to the common region of collagen XVIII revealed variable expression among cell lines of oral SCC. Conversely, the long form of collagen XVIII revealed no products. Comparatively, the lowest level of expression of CBP2/Hsp47 was observed in SCC4 that also had the lowest level of collagen XVIII. However, there was no direct relationship between the levels of CBP2/Hsp47 and collagen XVIII expression across the four cell lines. Treatment of SCC cells with CBP2/Hsp47 antisense phosphorothioate oligonucleotides modulated the production of collagen XVIII but not its expression. These findings imply that CBP2/Hsp47 may play a role in tumor progression by mediating the endogenous processing of collagen XVIII in tumor cells.
Ollins
Gabriel J
GJ
Department of Diagnostic Sciences and Pathology, Dental School, University of Maryland, Baltimore, 21201, USA.
Nikitakis
Nikolaos
N
Norris
Kathleen
K
Herbert
Carla
C
Siavash
Hessam
H
Sauk
John J
JJ
D020533:Angiogenesis Inhibitors / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D003094:Collagen / Q000235:genetics*; D043170:Collagen Type XVIII; D017931:DNA Primers; D043169:Endostatins; D015972:Gene Expression Regulation, Neoplastic; D050958:HSP47 Heat-Shock Proteins; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D009062:Mouth Neoplasms / Q000235:genetics / Q000473:pathology; D020319:Oligodeoxyribonucleotides, Antisense; D010446:Peptide Fragments / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D020533:Angiogenesis Inhibitors; D043170:Collagen Type XVIII; D017931:DNA Primers; D043169:Endostatins; D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D010446:Peptide Fragments; D011994:Recombinant Proteins; C494660:SERPINH1 protein, human; D003094:Collagen