Disease relevance of Figf

• VEGF-D was localized in tumor cells and endothelium in human non-small cell lung carcinoma and breast ductal carcinoma in situ [1].
• Here we studied figf expression during murine embryonic development. figf expression was detected with a dynamic pattern in several body structures and organs such as limb buds, acoustic ganglion, teeth, heart, anterior pituitary as well as lung and kidney mesenchyme, liver, derma, and periosteum of the vertebral column [2].
• The results indicate that the loss of NCAM function causes lymph node metastasis via VEGF-C- and VEGF-D-mediated lymphangiogenesis [3].
• When these mice were crossed to Rip1Tag2 mice, VEGF-D-expressing tumors also exhibited peritumoral lymphangiogenesis with lymphocyte accumulations and hemorrhages, and they frequently developed lymph node and lung metastases [4].
• In many human carcinomas, expression of the lymphangiogenic factor vascular endothelial growth factor-D (VEGF-D) correlates with up-regulated lymphangiogenesis and regional lymph node metastasis [4].

High impact information on Figf

• Staining with markers specific for lymphatic endothelium demonstrated that VEGF-D induced the formation of lymphatics within tumors [5].
• Vascular endothelial growth factor (VEGF)-C and VEGF-D have been shown to stimulate lymphangiogenesis and their receptor, VEGFR-3, has been linked to human hereditary lymphedema [6].
• Sprouting was rescued by VEGF-C and VEGF-D but not by VEGF, indicating VEGF receptor 3 specificity [7].
• This finding was unanticipated because lymphangiogenesis has been thought to be mediated by other members of the VPF/VEGF family, namely, VEGF-C and VEGF-D [8].
• Airway dendritic cells, macrophages, neutrophils, and epithelial cells expressed the VEGFR-3 ligands VEGF-C or VEGF-D [9].

Biological context of Figf

• The treatment of HUVECs with Figf/Vegf-D induces dose-dependent cell growth [10].
• This study demonstrates that RNA splicing, protein glycosylation, and proteolysis are mechanisms for generating structural diversity of mouse VEGF-D [11].
• Chimpanzee VEGFD promoter, cow Vegfd promoter, mouse Vegfd promoter and rat Vegfd promoter were identified within NW_121675.1, AC161065.2, AL732475.6 and AC130036.3 genome sequences, respectively [12].
• This suggests that VEGF-D may be of special relevance for the vascularization of lung tissue during the last trimester of fetal development [13].
• Transfection of exogenous c-fos driven by a constitutive promoter restores the FIGF expression in these cells [14].

Anatomical context of Figf

• The secreted glycoprotein vascular endothelial growth factor-D (VEGF-D) is angiogenic, lymphangiogenic, and promotes metastatic spread of tumor cells via lymphatic vessels [11].
• VEGF-D, expressed only by cadherin-11-positive cells of the mesenchyme, is first detected at embryonic day (E) 13.5, a period of active vasculogenesis [15].
• Mouse Vegfd mRNA was expressed in kidney, pregnant oviduct, and neural tissues [12].
• FIGF overexpression induces morphological alterations in fibroblasts [14].
• RESULTS: VEGF-D overexpressing clonal MCF-7 and MDA-MB-231 cell lines displayed increased proliferative activities and upregulation of cyclins A, D1 and D3, compared to the vector control [16].

Associations of Figf with chemical compounds

• Furthermore, in a solid phase binding assay recombinant VEGF-C and -D bound to purified alpha9beta1 integrin in a dose- and cation-dependent fashion showing that VEGF-C and VEGF-D are ligands for the integrin alpha9beta1 [17].
• Ca(2+) deprivation from the culture medium determined the loss of cadherin-11 from the cell surfaces and down-regulation of Vegf-D mRNA [18].

Regulatory relationships of Figf

• In addition we have shown that the VEGF homology domain of the structurally related growth factor VEGF-D is capable of binding to and activating VEGFR-2 but has no vascular permeability activity, indicating that VEGFR-2 binding does not correlate with permeability activity for all VEGF family members [19].
• This suggests that cell interaction mediated by cadherin-11 induces the expression of the angiogenic factor Vegf-D in fibroblasts [18].
• It is most likely, however, that the mechanisms by which VEGF-C promotes LN metastasis are different from those of VEGF-D [20].

Other interactions of Figf

• These results also suggest that the expression of FIGF in response to c-fos activation induces specific differentiation patterns and its aberrant activation contributes to the malignant phenotype of tumors [14].
• We show that in the long bones of newborn mice, VEGF-D and VEGFR-3 are expressed in the osteoblasts of the growing plate [21].

Analytical, diagnostic and therapeutic context of Figf

• Northern blot analysis shows that FIGF expression is strongly reduced in c-fos-deficient cells [14].
• By in situ hybridization we demonstrated that noninteracting fibroblasts express low levels of Vegf-D mRNA, whereas contacting cells express high levels of Vegf-D transcripts [18].
• We further addressed the biological function of VEGF-D for induction of lymphatic metastasis in a nude mouse xenograft model using two human ductal pancreatic cancer cell lines with overexpression of VEGF-D [22].
• The expression of VEGF-C and VEGF-D mRNAs and proteins were examined by reverse transcriptase-polymerase chain reaction and immunohistochemistry, respectively [23].

References