Angiogenic switch occurs during the precancerous stage of human esophageal squamous cell carcinoma

Kitadai, Yasuhiko; Onogawa, Seiji; Kuwai, Toshio; Matsumura, Shunji; Hamada, Hiroshige; Ito, Masanori; Tanaka, Shinji; Yoshihara, Masaharu; Chayama, Kazuaki

doi:10.3892/or.11.2.315

Cited by 28 publications

(24 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This was also indicated in work by Kitadai et al [117], who demonstrated an initial increase in vessel density and enhanced expression of VEGF and platelet-derived endothelial cell growth factor, another angiogenic factor, in dysplastic epithelium of esophageal squamous cell carcinomas. Auvinen et al [118] compared Barrett's dysplasia with normal esophageal mucosa, finding that Barrett's-specific glandular epithelium secretes VEGF-A, in addition to a mixture of sialomucin and sulfated mucins.…”

Section: The Role Of Vegf In Esophageal Cancermentioning

confidence: 51%

Activation of Growth Factor Receptors in Esophageal Cancer—Implications for Therapy

et al. 2007

View full text Add to dashboard Cite

Esophageal cancer is a highly aggressive disease and is the seventh most common cause of cancer-related death in the western world. Worldwide, it ranks as the sixth most frequent cause of cancer death. Despite advances in surgical techniques and treatment, the prognosis of esophageal cancer remains poor, with very few longterm survivors. The need for novel strategies to detect esophageal cancer earlier and to improve current therapy is urgent.It is well established that growth factors and growth factor receptor-mediated signaling pathways are important components of the transformation process in many forms of cancer, including esophageal cancer. With the recent advances in drug development, there are emerging possibilities to use growth factor signal transduction pathways in targeted therapy. This review provides a summary of the role of growth factors and their receptors in esophageal cancer and discusses their potential roles as biomarkers and as targets in therapy.

show abstract

Section: The Role Of Vegf In Esophageal Cancermentioning

confidence: 51%

Activation of Growth Factor Receptors in Esophageal Cancer—Implications for Therapy

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Vascular endothelial growth factor expression was elevated in epithelial cells with strong VEGFR-2 expression on associated vessels (Auvinen et al, 2002). Evidence of enhanced angiogenesis was also demonstrated in precursor lesions of oesophageal SCC accompanied by elevated VEGF and TP levels (Kitadai et al, 2004). Increased CD34 microvessel count and VEGF mRNA and protein expression was demonstrated in Helicobacter pylori-associated gastritis (Tuccillo et al, 2005).…”

Section: Gastrointestinal Tractmentioning

confidence: 80%

Angiogenesis in pre-malignant conditions

et al. 2008

View full text Add to dashboard Cite

Evidence from human studies suggests that angiogenesis commences during the pre-malignant stages of cancer. Inhibiting angiogenesis may, therefore, be of potential value in preventing progression to invasive cancer. Understanding the mechanisms inducing angiogenesis in these lesions and identification of those important in human tumourigenesis are necessary to develop translational strategies that will help realise the goal of angioprevention.

show abstract

“…28 Immunohistochemical analysis of angiogenic regulators in human breast pathologies highlights the complexity of angiogenic regulation with progression. 29 While there are large numbers of data published in model systems touting novel regulators of an 'angiogenic switch', for example, [30][31][32][33] it seems far more likely that in human disease there are complex opposing systems that gradually lead to an increased angiogenic phenotype as a function of epithelial progression and stromal response. We have shown this for breast cancer, 3 others have shown this for colon cancer.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of VEGFR2 prevents DMBA-induced mammary tumor formation

Heffelfinger

Yan

Gear

et al. 2004

Laboratory Investigation

View full text Add to dashboard Cite

Preinvasive mammary pathologies in humans and rat chemical carcinogenesis model systems have an increased microvascular density relative to normal tissue. This suggests the possibility of preventing invasive breast cancer by inhibiting angiogenesis. Vascular endothelial cell growth factor (VEGF) is a potent angiogenic growth factor, commonly involved in tumor-induced angiogenesis. Here, we show that both VEGF and VEGFR2 expression increase with histological progression to invasive disease in the rat 7,12-dimethylbenz [a]anthracene (DMBA) model. Other VEGF receptors, VEGFR1, neuropilin 1 and neuropilin 2, are constitutively expressed throughout progression. To examine whether VEGF signaling is functionally relevant to tumor-induced endothelial tubule formation in vitro and for tumor formation in vivo, we utilized the VEGFR2 inhibitor, ZD6474. In vitro endothelial cell tubulogenesis induced by isolated mammary organoids or carcinoma in situ from DMBA-treated rats is inhibited by ZD6474, in a dose-dependent fashion. The administration of ZD6474 to DMBAtreated rats inhibits the formation of atypical ductal hyperplasia and carcinoma in situ by greater than 95% (Po0.05), when administered 1 week or 6 weeks post-DMBA initiation. Invasive disease was absent in all ZD6474 cohorts. These data support the hypothesis that progression of DMBA-induced preinvasive mammary pathologies to palpable disease requires angiogenesis via a VEGF-dependent mechanism. Keywords: ZD6474; VEGF; VEGFR2; DMBA; chemoprevention Angiogenesis is the process of forming new vessels from pre-existing vessels, 1 and has been shown to be important in the process of breast cancer progression and metastasis. 2 We and others have shown that angiogenesis is also important in the process of breast cancer formation, as indicated by the stepwise increase in microvascular density with progression from normal epithelium to invasive disease. [3][4][5][6] In addition, we have shown that in the rat model system of DMBA-induced mammary tumor formation there is a similar pattern of upregulated microvascular density with progression. 7 Finally, if one isolates normal epithelium or tumor tissue from DMBA-treated rats, both are capable of inducing endothelial tubule formation in vitro, indicating that the angiogenic potential of these tissues is greater than that from vehicle-treated control rats. 7

show abstract

Angiogenic switch occurs during the precancerous stage of human esophageal squamous cell carcinoma

Cited by 28 publications

References 0 publications

Activation of Growth Factor Receptors in Esophageal Cancer—Implications for Therapy

Activation of Growth Factor Receptors in Esophageal Cancer—Implications for Therapy

Angiogenesis in pre-malignant conditions

Inhibition of VEGFR2 prevents DMBA-induced mammary tumor formation

Contact Info

Product

Resources

About