Expression levels of vascular endothelial growth factor, matrix metalloproteinases 2 and 9 and tissue inhibitor of metalloproteinases 1 and 2 in the plasma of patients with ovarian carcinoma

Manenti, Luigi; Paganoni, Paola; Floriani, Irene; Landoni, Fabio; Torri, Valter; Buda, Alessandro; Taraboletti, Giulia; Labianca, Roberto; Belotti, Dorina; Giavazzi, Raffaella

doi:10.1016/s0959-8049(03)00427-1

Cited by 89 publications

(85 citation statements)

References 34 publications

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“…MMP9 regulates VEGF bioavailability, and in turn, VEGF stimulates MMP9 expression. The high levels of VEGF and MMP9 found in the plasma and ascites of patients with ovarian carcinoma (10), and in the plasma and ascites of nude mice with human ovarian carcinoma xenografts (11), seems to confirm the importance of this mutual regulation in ovarian cancer progression.…”

Section: Discussionmentioning

confidence: 82%

“…VEGF, the most important proangiogenic factor, is primarily thought to contribute to ovarian tumor progression not only on account of its proangiogenic activity, but also through its ability to increase the permeability of diaphragmatic and tumor-associated vasculature, contributing to the formation of ascites. Previous studies have reported high levels of VEGF in the plasma and ascites of patients with ovarian carcinoma (10). VEGF levels correlate with the progression of the disease, and with response to chemotherapy in human ovarian carcinoma xenografts (11,12).…”

Section: Introductionmentioning

confidence: 98%

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Vascular Endothelial Growth Factor Stimulates Organ-Specific Host Matrix Metalloproteinase-9 Expression and Ovarian Cancer Invasion

Belotti

Calcagno

Garofalo

et al. 2008

Molecular Cancer Research

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Vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMP) regulate each other, contributing to tumor progression. We have previously reported that MMP9 induces the release of tumor VEGF, promoting ascites formation in human ovarian carcinoma xenografts. The aim of this study was to investigate whether tumor-derived VEGF regulated the expression of gelatinase by the stroma, influencing the invasive properties of ovarian tumors. Tumor variants derived from 1A9 human ovarian carcinoma, stably expressing VEGF 121 in the sense (1A9-VS-1) and antisense orientations (1A9-VAS-3), were used. In vivo, zymographic analysis of tumors from 1A9-VS-1 implanted in the peritoneal cavity of nude mice showed higher levels of gelatinases, particularly murine MMP9, indicating that VEGF stimulates host expression of the matrix-degrading enzyme. Murine MMP9 expression was also high in the ovaries of mice bearing 1A9-VS-1 tumors. The effect on host MMP9 activity was organ-specific. The levels of host pro-MMP9 in ovaries correlated with the plasma levels of tumor VEGF and with the selective invasion of the ovaries. Induction of host MMP9 expression in tumors and ovaries was independent of the site of tumor growth as it was seen in mice carrying both intraperitoneal and subcutaneous tumors. The anti-VEGF antibody bevacizumab (Avastin) inhibited MMP9 expression and tumor invasion in the ovaries of mice bearing 1A9-VS-1 tumors. These findings point to a complex cross-talk between VEGF and MMPs in the progression of ovarian tumor and suggest the possibility of using VEGF inhibitors to affect MMP-dependent tumor invasion.

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Section: Discussionmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 98%

Vascular Endothelial Growth Factor Stimulates Organ-Specific Host Matrix Metalloproteinase-9 Expression and Ovarian Cancer Invasion

Belotti

Calcagno

Garofalo

et al. 2008

Molecular Cancer Research

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“…Büyüme faktörleri ve sitokinlerin üretimi, spesifik proteinazlar aracılığıyla bazal membran yıkımı 32 , ovaryan kanser ile ilişkili anjiyogenez ve tümör yayılımından sorumludur. Bu yüzden bu faktörlerin tanımlanması teşhis ve tedavi için önemli bilgilerin elde edilmesini sağlar 27 . MMP-2 ve MMP-9 tüm bazal membranların komponenti olan tip IV kollajeni degrade etme yeteneğine sahiptir.…”

Section: Matriks Metalloproteinazlar Ve Anjiyogenik Faktörlerin Ovaryunclassified

“…Bununla birlikte, MMP-2 ve 9'un ovaryan kanser dokularında, asit sıvılarında ve kültüre edilmiş hücrelerde eksprese olduğu da belirtilmiştir. Deneysel çalışmalar, MMP-2 ve 9'un ovaryan kanser hücrelerinin invazyon ve metastazının ilerlemesinde önemli faktörler olduklarını göstermiş ve MMP inhibitörleri ile tedavi edilen ovaryan karsinoma ksenograftli hayvanlarda, daha az tümör ve asit oluşumu ve daha uzun yaşam süresi tespit edilmiştir 27 .…”

Section: Matriks Metalloproteinazlar Ve Anjiyogenik Faktörlerin Ovaryunclassified

Overlerde Anjiyogenezi Etkileyen Faktörler

Çelik¹,

Mete²

2017

Arşiv Kaynak Tarama Dergisi

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Angiogenesis is the process of new capillary formation from preexisting vessels that occurs in both the physiological and pathological processes in our body. Ovarian angiogenesis participates in normal ovarian physiologic activation, various ovarian diseases and neoplasms throughout the follicular and luteal phases of the ovarian cycle. The normal ovarian function modulated by a wide range of proangiogenic and antiangiogenic factors that directly affects angiogenesis. The most important of these factors are vascular endothelial growth factor, epidermal growth factor, fibroblast growth factor, angiotensin ıı, matrix metalloproteinases as well as many other factors are involved in this process. Today increased knowledge in this issues will enable the emergence of new therapeutic approaches in the understanding and treatment of pathogenesis of many diseases.

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“…Plasma VEGF levels are significantly higher in ovarian cancer patients than in normal controls or patients with benign disease [50]. In a recent study, Gorelik, et al demonstrated that a panel of five markers that included VEGF could detect ovarian cancer with a sensitivity of 84% at 95% specificity [25].…”

Section: Vascular Endothelial Growth Factor (Vegf)mentioning

confidence: 99%

Early Detection of Ovarian Cancer

Das

Bast

2008

Biomarkers Med.

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Abstract. Despite advances in therapy, ovarian cancer remains the most deadly of the gynecological cancers. Less than 30% of women with advanced stage disease survive long-term. When diagnosed in stage I, up to 90% of patients can be cured with conventional surgery and chemotherapy. At present, only 25% of ovarian cancers are detected in stage I due, in part, to the absence of specific symptoms and to lack of an effective screening strategy. Early detection of ovarian cancer might significantly improve the overall survival rate of women with ovarian cancer if 1) most cancers are clonal and unifocal, arising in the ovary rather than in the peritoneum, 2) metastatic disease results from progression of clinically detectable stage I lesions, and 3) cancers remain localized for a sufficient interval to permit cost-effective screening. Given the prevalence of ovarian cancer, strategies for early detection must have high sensitivity for early stage disease (>75%), but must have extremely high specificity (99.6%) to attain a positive predictive value of at least 10%. Transvaginal sonography (TVS), serum markers and a combination of the two modalities have been evaluated for early detection of ovarian cancer. Among the serum markers, CA125 has received the most attention, but lacks the sensitivity or specificity to function alone as a screening test. Greater specificity can be achieved by combining CA125 and TVS and/or by monitoring CA125 over time. Two stage screening strategies promise to be cost effective, where abnormal serum assays prompt TVS to detect lesions that require laparotomy. Accrual has been completed for a 200,000 woman trial in the United Kingdom that will test the ability of a rising CA125 to trigger TVS and subsequent exploratory surgery. Given the heterogeneity of ovarian cancer, it is unlikely that any single marker will be sufficiently sensitive to provide an effective initial screen. Sensitivity of serum assays might be enhanced by utilizing a panel of biomarkers. Candidate biomarkers have been discovered through empirical development of monoclonal antibodies, studies of gene expression, cloning of gene families and proteomic techniques. The development of technologies that measure multiple serum markers simultaneously, linked to the creation of statistical methods that enhance sensitivity without sacrificing specificity hold great promise.

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Expression levels of vascular endothelial growth factor, matrix metalloproteinases 2 and 9 and tissue inhibitor of metalloproteinases 1 and 2 in the plasma of patients with ovarian carcinoma

Cited by 89 publications

References 34 publications

Vascular Endothelial Growth Factor Stimulates Organ-Specific Host Matrix Metalloproteinase-9 Expression and Ovarian Cancer Invasion

Vascular Endothelial Growth Factor Stimulates Organ-Specific Host Matrix Metalloproteinase-9 Expression and Ovarian Cancer Invasion

Overlerde Anjiyogenezi Etkileyen Faktörler

Early Detection of Ovarian Cancer

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