C-fos-induced growth factor (FIGF) (or vascular endothelial growth factor D, VEGF-D) is a vascular endothelial growth factor that in humans is encoded by the FIGFgene.[1]
The protein encoded by this gene is a member of the platelet-derived growth factor/vascular endothelial growth factor (PDGF/VEGF) family and is active in angiogenesis, lymphangiogenesis, and endothelial cell growth. This secreted protein undergoes a complex proteolytic maturation, generating multiple processed forms that bind and activate VEGFR-2 and VEGFR-3 receptors. The structure and function of this protein is similar to those of vascular endothelial growth factor C.[1]
Tumor metastasis to lymph nodes
Lymph node metastasis is very often associated with several types of human malignancies. Cancer cells’ journey to lymph node takes place largely through lymphatic tunnel located in and around of primary tumor. VEGF-D's interactions with VEGFR-3 predominantly expressed in lymphatic vessels plays a key role in restructuring lymphatic channel and, hence, able to alter its functions related to fluid and cell transport along the conduits. VEGF-D has been established to be over-expressed in both tumor tissues and patients’ serum samples in several types of human cancer. In addition, VEGF-D expression has been implicated with increased incidence of regional lymph node metastasis. In experimental mice study, genetically modified tumor cell that was forced to produce VEGF-D protein have been established to boost up regional lymph nodes metastases.[2]
↑Stacker SA, Caesar C, Baldwin ME, Thornton GE, Williams RA, Prevo R, Jackson DG, Nishikawa S, Kubo H, Achen MG (Feb 2001). "VEGF-D promotes the metastatic spread of tumor cells via the lymphatics". Nature Medicine. 7 (2): 186–91. doi:10.1038/84635. PMID11175849.
Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID8125298.
Yamada Y, Nezu J, Shimane M, Hirata Y (Jun 1997). "Molecular cloning of a novel vascular endothelial growth factor, VEGF-D". Genomics. 42 (3): 483–8. doi:10.1006/geno.1997.4774. PMID9205122.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID9373149.
Rocchigiani M, Lestingi M, Luddi A, Orlandini M, Franco B, Rossi E, Ballabio A, Zuffardi O, Oliviero S (Jan 1998). "Human FIGF: cloning, gene structure, and mapping to chromosome Xp22.1 between the PIGA and the GRPR genes". Genomics. 47 (2): 207–16. doi:10.1006/geno.1997.5079. PMID9479493.
Stacker SA, Stenvers K, Caesar C, Vitali A, Domagala T, Nice E, Roufail S, Simpson RJ, Moritz R, Karpanen T, Alitalo K, Achen MG (Nov 1999). "Biosynthesis of vascular endothelial growth factor-D involves proteolytic processing which generates non-covalent homodimers". The Journal of Biological Chemistry. 274 (45): 32127–36. doi:10.1074/jbc.274.45.32127. PMID10542248.
Nakamura Y, Yasuoka H, Tsujimoto M, Yang Q, Imabun S, Nakahara M, Nakao K, Nakamura M, Mori I, Kakudo K (Feb 2003). "Prognostic significance of vascular endothelial growth factor D in breast carcinoma with long-term follow-up". Clinical Cancer Research. 9 (2): 716–21. PMID12576440.
Rissanen TT, Markkanen JE, Gruchala M, Heikura T, Puranen A, Kettunen MI, Kholová I, Kauppinen RA, Achen MG, Stacker SA, Alitalo K, Ylä-Herttuala S (May 2003). "VEGF-D is the strongest angiogenic and lymphangiogenic effector among VEGFs delivered into skeletal muscle via adenoviruses". Circulation Research. 92 (10): 1098–106. doi:10.1161/01.RES.0000073584.46059.E3. PMID12714562.
Funaki H, Nishimura G, Harada S, Ninomiya I, Terada I, Fushida S, Tani T, Fujimura T, Kayahara M, Shimizu K, Ohta T, Miwa K (2003). "Expression of vascular endothelial growth factor D is associated with lymph node metastasis in human colorectal carcinoma". Oncology. 64 (4): 416–22. doi:10.1159/000070301. PMID12759540.
Orlandini M, Semboloni S, Oliviero S (Nov 2003). "Beta-catenin inversely regulates vascular endothelial growth factor-D mRNA stability". The Journal of Biological Chemistry. 278 (45): 44650–6. doi:10.1074/jbc.M304255200. PMID12920128.
Kurahara H, Takao S, Maemura K, Shinchi H, Natsugoe S, Aikou T (Dec 2004). "Impact of vascular endothelial growth factor-C and -D expression in human pancreatic cancer: its relationship to lymph node metastasis". Clinical Cancer Research. 10 (24): 8413–20. doi:10.1158/1078-0432.CCR-04-0379. PMID15623620.
Fink AM, Kaltenegger I, Schneider B, Frühauf J, Jurecka W, Steiner A (Dec 2004). "Serum level of VEGF-D in patients with primary lymphedema". Lymphology. 37 (4): 185–9. PMID15693535.
Kaushal V, Mukunyadzi P, Dennis RA, Siegel ER, Johnson DE, Kohli M (Jan 2005). "Stage-specific characterization of the vascular endothelial growth factor axis in prostate cancer: expression of lymphangiogenic markers is associated with advanced-stage disease". Clinical Cancer Research. 11 (2 Pt 1): 584–93. PMID15701844.
Yasuoka H, Nakamura Y, Zuo H, Tang W, Takamura Y, Miyauchi A, Nakamura M, Mori I, Kakudo K (Aug 2005). "VEGF-D expression and lymph vessels play an important role for lymph node metastasis in papillary thyroid carcinoma". Modern Pathology. 18 (8): 1127–33. doi:10.1038/modpathol.3800402. PMID15803188.