Disease relevance of FIGF

• VEGF-D mRNA was significantly more abundant in normal tissues than in adenomas (p = 0.0001) and carcinomas (p < 0.0001) [1].
• RESULTS: We observed that expression patterns of VEGF isotypes corresponded to the prostate cancer stage: high expression of angiogenic growth factor VEGF-A was observed in early-stage prostate specimens, whereas high expression of lymphangiogenic growth factor VEGF-D was associated with advanced-stage metastatic disease [2].
• VEGF-D expression was detected only in an inflammatory breast cancer and a tumor which developed an inflammatory skin metastasis [3].
• VEGFD, implicated in angiogenesis and lymphatic metastasis, is a pharmacogenomics target in the field of oncology [4].
• However, VEGF-D levels were decreased in patients with cervical nodal metastasis as compared to patients with negative lymph node status [5].

Psychiatry related information on FIGF

• VEGF-D may be useful in the treatment of breast cancer as a decision-making biomarker for aggressive treatment after operation [6].

High impact information on FIGF

• Two of its family members, VEGF-C and VEGF-D, regulate the lymphatic endothelial cells via their receptor VEGFR-3 [7].
• The lymphangiogenic molecules VEGF-D and angiopoietin-2 were elevated in the plasma of individuals with acquired immune deficiency syndrome and Kaposi sarcoma [8].
• Plasmin activates the lymphangiogenic growth factors VEGF-C and VEGF-D [9].
• Expression of a truncated derivative of VEGF-D demonstrated that the receptor-binding capacities reside in the portion of the molecule that is most closely related in primary structure to other VEGF family members and that corresponds to the mature form of VEGF-C [10].
• VEGF-D does not bind to VEGFR-1 [10].

Chemical compound and disease context of FIGF

• The VEGF-D-expressing MCF-7 and MDA-MB-231 lines displayed resistance to apoptosis induced by hypoxia, staurosporin and cycloheximide [11].
• VEGF-D expression was enhanced by oestrogen in MCF-7 and T47D breast cancer cells, and was blocked by hydroxytamoxifen [12].
• CONCLUSION: These findings support a role for hypoxia and oestrogen induced VEGF-D in human breast cancer and also suggest that tamoxifen and related oestrogen antagonists may exert some of their antitumour effects through the abrogation of VEGF-D induced function [12].

Biological context of FIGF

• The FIGF promoter contains an optimal AP-1-binding site and lacks a canonical TATA box [13].
• The predicted amino acid sequence of FIGF is 84% identical to that of the mouse protein, and it is highly conserved (up to 40%) in the dimerization domain with respect to the VEGF members of the family [13].
• Human FIGF: cloning, gene structure, and mapping to chromosome Xp22.1 between the PIGA and the GRPR genes [13].
• Treatment of macrophages with VEGF-D induced apoptosis as determined by annexin V staining, by immunoblotting of activated caspase 3, and by the ratio of Bcl-2/Bax as well as by DNA fragmentation [14].
• At least five out of six bHLH-binding sites within human VEGFD proximal promoter region were conserved in chimpanzee VEGFD proximal promoter region, while only one in cow Vegfd proximal promoter region [4].

Anatomical context of FIGF

• In addition, VEGF-D is a mitogen for endothelial cells [10].
• In adult human tissues, VEGF-D mRNA is most abundant in heart, lung, skeletal muscle, colon, and small intestine [10].
• Interestingly, macrophages within inflammatory perivascular regions coexpressed Flt-4, VEGF-C and VEGF-D [14].
• METHODS AND RESULTS: Carotid artery thrombendartherectomy specimens from 10 patients with unstable plaque were stained for Flt-4 and its specific growth factors VEGF-C and VEGF-D [14].
• In vitro studies confirmed the expression of Flt-4, VEGF-C and VEGF-D in human monocytes and cultured macrophages [14].

Associations of FIGF with chemical compounds

• Another tyrosine kinase receptor, VEGFR-3 (flt-4) binds VEGF-C and VEGF-D and is more important in the development of lymphatic vessels [15].
• Treatment of NB cells with retinoic acid did not lead to a change in VEGF-C or VEGF-D mRNA expression [16].
• Only after in vitro incubation with tumor necrosis factor-alpha, lipopolysaccharide, or VEGF-D did these monocytes start to synthesize VEGF-C de novo [17].
• EXPERIMENTAL DESIGN: Nitrite/nitrate levels and VEGF-D production were assessed in K1 papillary thyroid carcinoma cells after induction and/or inhibition of nitric oxide (NO) synthesis [18].
• RESULTS: The production of nitrite/nitrate and VEGF-D in K1 cells was increased by treatment with the NO donor, (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA NONOate) [18].

Regulatory relationships of FIGF

• Their CM VEGF-C and VEGF-D increase in response to plasma cell CM and trigger plasma cell proliferation via VEGFR-3 [19].
• VEGF-C was detected in all carcinomas and dysplastic lesions that expressed VEGF-D [20].

Other interactions of FIGF

• We have identified a member of the VEGF family by computer-based homology searching and have designated it VEGF-D [10].
• VEGF-C and VEGF-D are ligands for VEGF receptor-3, which is expressed in the endothelium of lymphatic vessels [3].
• VEGF-B mRNA correlated with an infiltrative margin (p = 0.04) but no other clinicopathological variable, and expression of VEGF-D demonstrated no association with any parameter examined [1].
• Adenoviral overexpression of VEGF receptor-2 ligands, VEGF-A and the mature form of VEGF-D, enlarge the preexisting capillaries in skeletal muscle and myocardium via nitric oxide(NO)-mediated mechanisms and via proliferation of both endothelial cells and pericytes, resulting in markedly increased tissue perfusion [21].
• However, in contrast to control synovial lining, little if any VEGF-D was detected in AS or RA synovial lining [22].

Analytical, diagnostic and therapeutic context of FIGF

• Fluorescence in situ hybridization mapped FIGF to chromosomal region Xp22 [13].
• EXPERIMENTAL DESIGN: The levels of VEGF-A and VEGF-D mRNA in early- and advanced-stage specimens were compared using an angiogenic gene array and were confirmed by quantitative real-time PCR [2].
• We assessed the presence of vascular endothelial growth factor (VEGF)-C, VEGF-D and their receptor VEGFR-3 by immunohistochemistry in 59 epithelial ovarian carcinomas, 11 borderline tumours and 20 benign cystadenomas [23].
• VEGF-C and VEGF-D mRNA were quantified by real-time reverse transcriptase-polymerase chain reaction [24].
• Survival curves determined by the Kaplan-Meier method and univariate analysis demonstrated that positive VEGF-D was associated with both disease-free survival (P = 0.0023) and overall survival (P = 0.0222) [6].

References