C-fos-induced growth factor explained

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 FIGF gene.^[1]

Function

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.

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]

Further reading

• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . Jan 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Orlandini M, Marconcini L, Ferruzzi R, Oliviero S . Identification of a c-fos-induced gene that is related to the platelet-derived growth factor/vascular endothelial growth factor family . Proceedings of the National Academy of Sciences of the United States of America . 93 . 21 . 11675–80 . Oct 1996 . 8876195 . 38117 . 10.1073/pnas.93.21.11675 . free . 1996PNAS...9311675O .
• Yamada Y, Nezu J, Shimane M, Hirata Y . Molecular cloning of a novel vascular endothelial growth factor, VEGF-D . Genomics . 42 . 3 . 483–8 . Jun 1997 . 9205122 . 10.1006/geno.1997.4774 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . Oct 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Achen MG, Jeltsch M, Kukk E, Mäkinen T, Vitali A, Wilks AF, Alitalo K, Stacker SA . Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk1) and VEGF receptor 3 (Flt4) . Proceedings of the National Academy of Sciences of the United States of America . 95 . 2 . 548–53 . Jan 1998 . 9435229 . 18457 . 10.1073/pnas.95.2.548 . 1998PNAS...95..548A . free .
• Rocchigiani M, Lestingi M, Luddi A, Orlandini M, Franco B, Rossi E, Ballabio A, Zuffardi O, Oliviero S . Human FIGF: cloning, gene structure, and mapping to chromosome Xp22.1 between the PIGA and the GRPR genes . Genomics . 47 . 2 . 207–16 . Jan 1998 . 9479493 . 10.1006/geno.1997.5079 .
• Stacker SA, Stenvers K, Caesar C, Vitali A, Domagala T, Nice E, Roufail S, Simpson RJ, Moritz R, Karpanen T, Alitalo K, Achen MG . Biosynthesis of vascular endothelial growth factor-D involves proteolytic processing which generates non-covalent homodimers . The Journal of Biological Chemistry . 274 . 45 . 32127–36 . Nov 1999 . 10542248 . 10.1074/jbc.274.45.32127 . free .
• Nakamura Y, Yasuoka H, Tsujimoto M, Yang Q, Imabun S, Nakahara M, Nakao K, Nakamura M, Mori I, Kakudo K . Prognostic significance of vascular endothelial growth factor D in breast carcinoma with long-term follow-up . Clinical Cancer Research . 9 . 2 . 716–21 . Feb 2003 . 12576440 .
• Yokoyama Y, Charnock-Jones DS, Licence D, Yanaihara A, Hastings JM, Holland CM, Emoto M, Umemoto M, Sakamoto T, Sato S, Mizunuma H, Smith SK . Vascular endothelial growth factor-D is an independent prognostic factor in epithelial ovarian carcinoma . British Journal of Cancer . 88 . 2 . 237–44 . Jan 2003 . 12610509 . 2377043 . 10.1038/sj.bjc.6600701 .
• 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 . VEGF-D is the strongest angiogenic and lymphangiogenic effector among VEGFs delivered into skeletal muscle via adenoviruses . Circulation Research . 92 . 10 . 1098–106 . May 2003 . 12714562 . 10.1161/01.RES.0000073584.46059.E3 . 17360574 .
• Funaki H, Nishimura G, Harada S, Ninomiya I, Terada I, Fushida S, Tani T, Fujimura T, Kayahara M, Shimizu K, Ohta T, Miwa K . Expression of vascular endothelial growth factor D is associated with lymph node metastasis in human colorectal carcinoma . Oncology . 64 . 4 . 416–22 . 2003 . 12759540 . 10.1159/000070301 . 45760526 .
• Orlandini M, Semboloni S, Oliviero S . Beta-catenin inversely regulates vascular endothelial growth factor-D mRNA stability . The Journal of Biological Chemistry . 278 . 45 . 44650–6 . Nov 2003 . 12920128 . 10.1074/jbc.M304255200 . free .
• McColl BK, Baldwin ME, Roufail S, Freeman C, Moritz RL, Simpson RJ, Alitalo K, Stacker SA, Achen MG . Plasmin activates the lymphangiogenic growth factors VEGF-C and VEGF-D . The Journal of Experimental Medicine . 198 . 6 . 863–8 . Sep 2003 . 12963694 . 2194198 . 10.1084/jem.20030361 .
• Vlahakis NE, Young BA, Atakilit A, Sheppard D . The lymphangiogenic vascular endothelial growth factors VEGF-C and -D are ligands for the integrin alpha9beta1 . The Journal of Biological Chemistry . 280 . 6 . 4544–52 . Feb 2005 . 15590642 . 1368959 . 10.1074/jbc.M412816200 . free .
• Kurahara H, Takao S, Maemura K, Shinchi H, Natsugoe S, Aikou T . 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 . Dec 2004 . 15623620 . 10.1158/1078-0432.CCR-04-0379 . 22659900 .
• Fink AM, Kaltenegger I, Schneider B, Frühauf J, Jurecka W, Steiner A . Serum level of VEGF-D in patients with primary lymphedema . Lymphology . 37 . 4 . 185–9 . Dec 2004 . 15693535 .
• Kaushal V, Mukunyadzi P, Dennis RA, Siegel ER, Johnson DE, Kohli M . 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 . Jan 2005 . 10.1158/1078-0432.584.11.2 . 15701844 .
• Yasuoka H, Nakamura Y, Zuo H, Tang W, Takamura Y, Miyauchi A, Nakamura M, Mori I, Kakudo K . VEGF-D expression and lymph vessels play an important role for lymph node metastasis in papillary thyroid carcinoma . Modern Pathology . 18 . 8 . 1127–33 . Aug 2005 . 15803188 . 10.1038/modpathol.3800402 . free .

Notes and References

1. Web site: Entrez Gene: FIGF c-fos induced growth factor (vascular endothelial growth factor D).
2. Stacker SA, Caesar C, Baldwin ME, Thornton GE, Williams RA, Prevo R, Jackson DG, Nishikawa S, Kubo H, Achen MG . VEGF-D promotes the metastatic spread of tumor cells via the lymphatics . Nature Medicine . 7 . 2 . 186–91 . Feb 2001 . 11175849 . 10.1038/84635 . 24131240 .