Modulation of cellular invasion by VEGF-C expression in squamous cell carcinoma of the head and neck.
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).


METHODS
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.


METHODS
An academic hospital laboratory.


METHODS
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.
Bock
Jonathan M
JM
Department of Otolaryngology-Head & Neck Surgery, University of Iowa Hospitals & Clinics, 200 Hawkins Dr, Iowa City, IA 52242, USA.
Sinclair
Lori L
LL
Bedford
Nichole S
NS
Jackson
Robert E
RE
Lee
John H
JH
Trask
Douglas K
DK
D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002465:Cell Movement; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D014161:Transduction, Genetic; D042582:Vascular Endothelial Growth Factor C / Q000502:physiology*
D042582:Vascular Endothelial Growth Factor C