Vascular endothelial growth factor C and vascular endothelial growth factor receptor 3 expression in squamous cell carcinomas of the head and neck

Neuchrist, Csilla; Erovic, Boban M.; Handisurya, Alessandra; Fischer, Michael B.; Steiner, Georg; Hollemann, David; Gedlicka, Claudia; Saaristo, Anne; Burian, Martin

doi:10.1002/hed.10235

Cited by 109 publications

(74 citation statements)

References 36 publications

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“…Previous reports 25,26 demonstrated the existence of VEGF receptors in head and neck squamous cell carcinoma cells, along with a predominant overexpression of VEGFR-2. This is in agreement with our results.…”

Section: Discussionmentioning

confidence: 87%

“…Similar paracrine action between cancer cells and stromal cells that infiltrate the tumor was previously described. 26 Some limitations of our study should be discussed. First, the sample size is limited and does not allow the performance of multivariate analysis.…”

Section: Discussionmentioning

confidence: 94%

“…30,31 VEGF receptors are mainly expressed in tumor vasculature; 9 but their expression in cancer cells was also described. 25,26 Our aim was to evaluate their expression on the tumor cells, in a quantitative way. The intensity of the membranous-cytoplasmic immunohistochemical staining was evaluated as follows: À, negative, þ , focal expression o5% of cancer cells, and þ þ , diffuse expression 45% of cancer cells.…”

Section: Antibody Expressionmentioning

confidence: 99%

“…[17][18][19][20][21][22][23][24] There are also studies describing the existence of VEGF receptors in cancer cell lines and in limited number of tissue samples in head and neck squamous cell carcinoma. 25,26 These observations suggest that VEGF can function as an autocrine growth factor. This hypothesis was experimentally confirmed both for solid tumors (such as prostate adenocarcinoma) 24 and also for hematological malignancies (such as acute leukemia).…”

mentioning

confidence: 96%

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Potential autocrine function of vascular endothelial growth factor in head and neck cancer via vascular endothelial growth factor receptor-2

et al. 2005

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Vascular endothelial growth factor is a peptide with well-defined actions on the vasculature and fundamental role in tumor angiogenesis. Its action in vascular endothelium is exerted in a paracrine manner. The immunohistochemical expression of this protein by cancer cells in head and neck squamous cell carcinoma was correlated with increased tumor aggressiveness and poor survival in previous studies. In the past years, an increasing amount of studies demonstrated potential autocrine action of vascular endothelial growth factor in various neoplasms. However, the existence and the impact of such autocrine action in head and neck cancer have not been demonstrated yet. In this retrospective study, we evaluated the expression of vascular endothelial growth factor and its receptors in neoplastic cells, in a cohort of patients with head and neck squamous cell carcinoma, and compared this expression with tumor aggressiveness, clinicopathologic parameters and outcome. High expression of vascular endothelial growth factor was strongly correlated with high expression of vascular endothelial growth factor receptor-2 (but not vascular endothelial growth factor receptor-1) on the cancer cells (Po0.001). The co-overexpression of both the protein and vascular endothelial growth factor receptor-2 was associated with higher tumor proliferation rate (Po0.001). The above cooverexpression also correlated with worse survival (log rank Po0.05) in patients with oral-larynx squamous cell carcinoma. Our results suggest that an autocrine vascular endothelial growth factor loop, mediated via vascular endothelial growth factor receptor-2, probably exists in head and neck squamous cell carcinoma. These observations support the hypothesis that the use of vascular endothelial growth factor receptor-2 inhibitors as adjuvant antiangiogenic therapy might have beneficial effects for these patients, by disrupting both paracrine (endothelial-dependent) and autocrine actions of vascular endothelial growth factor.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 94%

Section: Antibody Expressionmentioning

confidence: 99%

mentioning

confidence: 96%

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Potential autocrine function of vascular endothelial growth factor in head and neck cancer via vascular endothelial growth factor receptor-2

et al. 2005

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“…Among the angiogenic cytokines, VEGF-C draws special attention because of its potential involvement in the lymph node metastasis of several cancers includingcolorectal cancer, human pancreatic endocrine tumors, esophageal carcinomas, head and neck squamous cell carcinoma, uterine cervical cancer, primary non-smallcell lung cancer, gastric carcinoma, and laryngeal squamous carcinoma (Yonemura et al, 1999;Hashimoto et al, 2001;Kimura et al, 2003;Neuchrist et al, 2003;Jia et al, 2004;Sipos et al, 2004;Wang et al, 2004). Recently, Tsurusaki et al reported a significant correlation between the expression of VEGF-C and lymph node dissemination in human prostate carcinoma (Tsurusaki et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Upregulation of VEGF-C by androgen depletion: the involvement of IGF-IR-FOXO pathway

Wang

Rinaldo

et al. 2005

Oncogene

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

Bock

Sinclair²,

Bedford³

et al. 2008

Arch Otolaryngol Head Neck Surg

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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.

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Vascular endothelial growth factor C and vascular endothelial growth factor receptor 3 expression in squamous cell carcinomas of the head and neck

Cited by 109 publications

References 36 publications

Potential autocrine function of vascular endothelial growth factor in head and neck cancer via vascular endothelial growth factor receptor-2

Potential autocrine function of vascular endothelial growth factor in head and neck cancer via vascular endothelial growth factor receptor-2

Upregulation of VEGF-C by androgen depletion: the involvement of IGF-IR-FOXO pathway

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

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