Endostatin inhibits migration and invasion of head and neck squamous cell carcinoma cells.
Head and neck cancers are significant due to their high morbidity and associated complications. We report, for the first time, that endostatin directly affects epithelial lineage human cells derived from tumors of patients with head and neck squamous cell carcinoma (HNSCC). This study investigated endostatin's effects on several HNSCC cellular functions that are essential for tumor progression. We determined that exposure of HNSCC cells to endostatin activated the transcription-activating factors, NF-xB and AP-1 in a cell-line-dependent fashion. Endostatin also down-regulated the gene expression of several pro-migratory molecules. Migration and invasion assays showed that endostatin significantly inhibited these functions that are essential for tumor progression. Fluorescent labeling studies showed endostatin co-localized to tropomysin-binding HNSCC the microfilaments, suggesting endostatin's suppression of HNSCC cell migration and invasion may reflect perturbation of the microfilament function. Our data imply that endostatin's clinical efficacy extends beyond angiostatic properties to encompass a direct anti-tumorigenic effect against HNSCC cells.
Wilson
Ralph F
RF
Departments of Oral Maxillofacial Surgery and Pathology and Periodontology, College of Dentistry, Ohio State University, Columbus, Ohio, USA.
Morse
Mark A
MA
Pei
Ping
P
Renner
Robert J
RJ
Schuller
David E
DE
Robertson
Fredika M
FM
Mallery
Susan R
SR
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects; D003094:Collagen / Q000378:metabolism / Q000494:pharmacology*; D003864:Depression, Chemical; D043169:Endostatins; D004815:Epidermal Growth Factor / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D016023:Integrins / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D053506:Matrix Metalloproteinase 10; D008666:Metalloendopeptidases / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis / Q000235:genetics; D014062:Tongue Neoplasms / Q000473:pathology*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014335:Tropomyosin / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects
D000970:Antineoplastic Agents; D043169:Endostatins; D016023:Integrins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D018808:Transcription Factor AP-1; D014335:Tropomyosin; D019716:Tissue Inhibitor of Metalloproteinase-2; D004815:Epidermal Growth Factor; D003094:Collagen; D008666:Metalloendopeptidases; D053506:Matrix Metalloproteinase 10