Modulation of Cellular Invasion by VEGF-C Expression in Squamous Cell Carcinoma of the Head and Neck

Abstract

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.

A Hybrid Model Describing Different Morphologies of Tumor Invasion Fronts

“…T 0 therefore corresponds to the basal motility of tumor cells, while T 0 /h is their asymptotic motility for saturating concentrations of chemicals. The above hypothesis are in agreement with experimental observations providing, through classical wound healing experiments, that high concentrations of growth factors stimulate the migratory capacity of different tumor cell lines (see for example [18,19] for the Hepatocyte Growth Factor, [9,69] for the Vascular Endothelial Growth Factor families, and [65] for the Fibroblast Growth Factor).…”

Effect of Lymphangiogenic Factors on Survival in a Murine Model of Oral Squamous Cell Carcinoma

“…구강암과 대부분의 OSCC 세포주에서 VEGF 발현이 관찰되는 것으로 보고되었고 [4], 특히 VEGF-A와 VEGF-C가 중요한 조절자 의 역할을 하는 것으로 여겨진다 [5]. VEGF-A는 VEGFR-1, VEGFR-2와 작용하여 내피세포의 성장과 분화, 이주를 강화시키 고, 혈관의 투과성을 증가시킨다.…”

Modulação da expressão de VEGF-C por mediador relacionado ao estresse em culturas de carcinomas espinocelulares de boca

“…A relação dos mediadores do estresse com a angiogênese tumoral tem sido investigada, principalmente, com base na atividade do fator de crescimento endotelial vascular do tipo A (FREDRIKSSON et al, 2000;THAKER et al, 2006;YANG et al, 2006;YANG et al, 2008;GUO et al, 2009;YANG et al, 2009; Os membros da família VEGF são reguladores centrais da angiogênese e linfangiogênese tumoral e tem sido correlacionado com a ocorrência de metástases por meio da invasão de células malignas tanto nos vasos sanguíneos como nos linfáticos O-CHAROENRAT;MANN;STACKER, 2006;HIRAKAWA et al, 2007;SU et al, 2007;WARBURTON et al, 2007;STACKER, 2008;BOCK et al, 2008;DAS;SKOBE, 2008;SIRIWARDENA et al, 2008;SUGIURA et al, 2009). HIRAKAWA et al, 2007;SU et al, 2007;WARBURTON et al, 2007;STACKER, 2008;BOCK et al, 2008;DAS;SKOBE, 2008;SIRIWARDENA et al, 2008;.…”

“…A presença de receptores beta-adrenérgicos (β-ARs) e sua expressiva resposta ao estímulo da norepinefrina foram identificadas em várias linhagens de células tumorais (FREDRIKSSON et al, 2000;THAKER et al, 2006;YANG et al, 2006;YANG et al, 2008;GUO et al, 2009) SOOD et al, 2006;YANG et al, 2006;FLINT et al, 2007;CHAN;LIN;LIN, 2008;LIU et al, 2008;ARMAIZ-PENA et al, 2009;YANG et al, 2009;YAO et al, 2009 THAKER et al, 2006), em mieloma múltiplo (YANG et al, 2008), em melanoma (YANG et al, 2009) HIRAKAWA et al, 2007;SU et al, 2007;WARBURTON et al, 2007;STACKER, 2008;BOCK et al, 2008;DAS;SKOBE, 2008;SIRIWARDENA et al, 2008;SUGIURA et al, 2009).…”

“…Assim sendo, tem sido mostrada uma forte associação do VEGF-C com a ocorrência de metástase linfonodal e consequentemente com a progressão tumoral (O-CHAROENRAT; RHYS-EVANS; LI et al, 2006;WARBURTON et al, 2007;SIRIWARDENA et al, 2008;SUGIURA et al, 2009), influenciando diretamente o prognóstico do paciente BOCK et al, 2008). SCHULLER, 2007;FITZGERALD, 2009;SHANG;LIANG, 2009;YANG et al, 2009;BERNABÉ et al, 2011 LIANG, 2009;ZHANG et al, 2009;SHAHZAD et al, 2010;BERNABÉ et al, 2011 LIANG, 2009;ZHANG et al, 2009;SHAHZAD et al, 2010;BERNABÉ et al, 2011 …”