Circulating plasma vascular endothelial growth factor in mice bearing human ovarian carcinoma xenograft correlates with tumor progression and response to therapy

Manenti, Luigi; Riccardi, Elena; Marchini, Sergio; Naumova, Elitza; Floriani, Irene; Garofalo, Angela; Dossi, Romina; Marrazzo, Eleonora; Ribatti, Doménico; Scanziani, Eugenio; Bani, Maria Rosa; Belotti, Dorina; Broggini, Massimo; Giavazzi, Raffaella

doi:10.1158/1535-7163.mct-04-0305

Cited by 27 publications

(18 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is interesting to note that mice inoculated intraperitoneally with parental A2780 cells do not typically develop ascites and that overexpression of DLX4 in these cells, although able to induce VEGF levels, did not result in ascites. Manenti and colleagues 37 reported formation of ascites in mice inoculated intraperitoneally with A2780 cells that were stably transfected with VEGF. It should be noted that the levels of VEGF released by transfected A2780 cells in that study were very high (averaging 12,790 pg/ml), whereas levels released by our DLX4-transfected A2780 cell lines under the same culture conditions as the previous study were 200 to 250 pg/ml.…”

Section: Discussionmentioning

confidence: 99%

A Homeobox Gene Related to Drosophila Distal-Less Promotes Ovarian Tumorigenicity by Inducing Expression of Vascular Endothelial Growth Factor and Fibroblast Growth Factor-2

Hara

Samuel

Liu

et al. 2007

The American Journal of Pathology

View full text Add to dashboard Cite

Homeobox genes control developmental patterning and are increasingly being found to be deregulated in tumors. The DLX4 homeobox gene maps to the 17q21.3-q22 region that is amplified in some epithelial ovarian cancers. Because amplification of this region correlates with poor prognosis, we investigated whether DLX4 overexpression contributes to aggressive behavior of this disease. DLX4 was not detected in normal ovary and cystadenomas, whereas its expression in ovarian carcinomas was strongly associated with high tumor grade and advanced disease stage. Overexpression of DLX4 in ovarian cancer cells promoted growth in low serum and colony formation. Homeobox genes constitute an evolutionarily conserved superfamily of genes that play essential roles in controlling cell differentiation and morphogenesis during embryonic development.1 Members of this gene superfamily encode transcription factors and have been increasingly reported to be up-or down-regulated in a variety of cancers.2,3 Although the functional significance of many of these genes to tumor progression has yet to be defined, recent studies indicate that their aberrant expression promotes self-renewal, cell proliferation, and survival.2,3 For example, HOXA5 regulates the p53 promoter and its expression is lost in Ͼ60% of breast cancers. 4 On the other hand, overexpression of SIX1 in breast cancers induces cyclin A1 and deregulates cell cycle control. 5Various mechanisms give rise to aberrant homeobox gene expression in tumors. NKX3.1 maps to a region that frequently undergoes loss of heterozygosity in prostate intraepithelial neoplasia and prostate cancers, and NKX3.1 loss is thought to be an important initiating event in prostate neoplasia. 6,7 Loss of expression of HOXA5 in breast cancers and of HOXA10 in endometrial cancers has been attributed to promoter methylation. 4,8 Deregulation of many homeobox genes in leukemias is attributable to chromosomal translocations.3 Very few reports attribute overexpression of homeobox genes in solid tumors to gene amplification. One notable example is amplifications within the 17q21-q22 region that occur in ϳ10% of breast and ovarian cancers and are associated with poor prognosis. 9 -11 This region contains the HOXB gene cluster. HOXB7 and HOXB13 are members of this cluster and are overexpressed in breast and ovarian cancers.12-15 HOXB13 has been reported to promote invasiveness of breast and ovarian epithelial cells.

show abstract

Section: Discussionmentioning

confidence: 99%

A Homeobox Gene Related to Drosophila Distal-Less Promotes Ovarian Tumorigenicity by Inducing Expression of Vascular Endothelial Growth Factor and Fibroblast Growth Factor-2

Hara

Samuel

Liu

et al. 2007

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…Ovaries of 1A9-VS-1, but not 1A9-VAS-3 tumor -bearing mice, presented severe dilation of vessels (angiectasis) that correlated with the high VEGF plasma levels (12) and with the presence of inflammatory cells in the ovaries (Fig. 5A).…”

Section: Tumor-derived Vegf Influences Gelatinase Expression In Endotmentioning

confidence: 98%

“…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). VEGF inhibitors reduce ascites formation and dissemination in experimental ovarian tumor models (13).…”

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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…Even direct transfection of mouse peritoneum with VEGF is sufficient to cause an accumulation of ascites [67]. In contrast, transfection of tumor cell lines with VEGF antisense oligonucleotides resulted in reduced formation of malignant effusions in the mouse [63,68,70]. Altogether, these collected findings allow for the firm conclusion that local VEGF secretion is responsible, in a large part, for initiating and maintaining the ascites pattern of tumor growth.…”

Section: Vascular Endothelial Growth Factor As a Key Factor For The Imentioning

confidence: 99%

Intraperitoneal VEGF Inhibition Using Bevacizumab: A Potential Approach for the Symptomatic Treatment of Malignant Ascites?

et al. 2009

View full text Add to dashboard Cite

Despite overall improvements in oncological care in the palliative setting, symptomatic malignant ascites remains a severe clinical problem. This form of effusion is known to be widely resistant to established modes of systemic therapy. Accordingly, frequent paracentesis often represents the only effective way for symptom relief in patients with advanced cancer. This invasive mode of therapy, however, is often very burdensome for the patient who is already severely distressed by the underlying malignancy. Recently, the trifunctional monoclonal antibody catumaxomab given i.p. has shown symptom relief in patients with ovarian cancer and malignant ascites. On another front, the release of vascular endothelial growth fac-

show abstract

Circulating plasma vascular endothelial growth factor in mice bearing human ovarian carcinoma xenograft correlates with tumor progression and response to therapy

Abstract: Vascular endothelial growth factor

Cited by 27 publications

References 39 publications

A Homeobox Gene Related to Drosophila Distal-Less Promotes Ovarian Tumorigenicity by Inducing Expression of Vascular Endothelial Growth Factor and Fibroblast Growth Factor-2

A Homeobox Gene Related to Drosophila Distal-Less Promotes Ovarian Tumorigenicity by Inducing Expression of Vascular Endothelial Growth Factor and Fibroblast Growth Factor-2

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

Intraperitoneal VEGF Inhibition Using Bevacizumab: A Potential Approach for the Symptomatic Treatment of Malignant Ascites?

Contact Info

Product

Resources

About