Modulation of cellular invasion by VEGF-C expression in squamous cell carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg 2008 Apr;134(4):355-62
Date
04/23/2008Pubmed ID
18427000DOI
10.1001/archotol.134.4.355Scopus ID
2-s2.0-42549155418 (requires institutional sign-in at Scopus site) 23 CitationsAbstract
OBJECTIVE: To determine how vascular endothelial growth factor C (VEGF-C) affects tumor cell invasion and motility in squamous cell carcinoma of the head and neck (SCCHN).
DESIGN: A molecular biology study. The VEGF-C coding sequence was cloned into an expression vector and stably transfected into the SCCHN cell line SCC116 to create the SCC116-VEGFC line. RNA interference (RNAi) was used to block VEGF-C expression. An adenoviral system for expressing VEGF-C RNAi was developed and tested.
SETTING: An academic hospital laboratory.
MAIN OUTCOME MEASURES: Relative VEGF-C RNA levels were determined by real-time quantitative reverse transcriptase-polymerase chain reaction, and protein expression was evaluated by Western blot. Cellular invasion was evaluated by 24-hour semipermeable membrane transit assay.
RESULTS: SCC116-VEGFC cells had markedly increased expression of VEGF-C protein and RNA compared with normal SCC116 controls. SCC116-VEGFC cells produced marked increases in cellular invasion and motility compared with SCC116 cells. Blockade of VEGF-C expression by transfection of a VEGF-C RNAi expression plasmid into both SCC116 and SCC116-VEGFC cells induced a 38% decrease in SCCHN invasion and motility as tested by a semipermeable membrane invasion assay. We developed an adenoviral expression system for VEGF-C RNAi, which also induced a dose-dependent decrease in cellular invasion in the highly invasive DM12 cell line.
CONCLUSIONS: These studies demonstrate that intracellular VEGF-C levels modulate in vitro SCCHN motility and invasion. Further work is needed to clarify the specific receptors and signaling pathways that are involved in SCCHN motility. Molecular therapies that inhibit the VEGF-C pathway may have clinical potential in the treatment of lymphatic metastasis in SCCHN.
Author List
Bock JM, Sinclair LL, Bedford NS, Jackson RE, Lee JH, Trask DKAuthor
Jonathan Bock MD Professor in the Otolaryngology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Carcinoma, Squamous CellCell Culture Techniques
Cell Line, Tumor
Cell Movement
Head and Neck Neoplasms
Humans
Neoplasm Invasiveness
RNA Interference
Transduction, Genetic
Vascular Endothelial Growth Factor C
