Moléculas moduladoras de vías de señalización basales y desencadenadas por el Factor de Crecimiento Derivado de Plaquetas (PDGF) en un modelo celular de fibrosarcoma humano

Palabras clave: fibrosarcoma, PDGF-BB, PDGFRb, MAPK, PI3K/Akt, péptidos sintéticos, PD98059

Resumen

La sobreexpresión del Factor de Crecimiento Derivado de Plaquetas (PDGF) y sus receptores ha sido relacionada con el desarrollo de patologías asociadas a la pérdida del control de la proliferación, como el cáncer, principalmente sarcomas de tejidos blandos y gliomas. Por lo anterior, el desarrollo de agentes terapéuticos que inhiban las respuestas biológicas desencadenadas por estas moléculas han sido blanco de estudios preclínicos en diferentes tipos de cáncer. En este sentido, el objetivo de este estudió fue evaluar el efecto de dos péptidos sintetizados a partir del ligando natural de la isoforma PDGF-BB, así como de inhibidores específicos de proteínas intracelulares, sobre la activación de moduladores de las vías de señalización PI3K/Akt y MAPK basales y dependientes de PDGF y sobre el fenotipo proliferativo de la línea celular HT1080.

Descargas

La descarga de datos todavía no está disponible.

Citas

Raica M, Cimpean A. Platelet-derived growth factor (PDGF)/PDGF receptors (PDGFR) axis as target for antitumor and antiangiogenic therapy. Pharmaceuticals. 2010;3(3):572-599.

Yu J, Ustach C, Kim H. Platelet-derived growth factor signaling and human cancer. J. Biochem Mol Biol. 2003;36(1):49-59.

Fredriksson L, Li H, Eriksson U. The PDGF family: four gene products form five dimeric isoforms. Cytokine Growth Factor Rev. 2004;15(4):197-204.

Heldin C, Westermark B. Mechanism of action and in vivo role of platelet-derived growth factor. Physiol Rev. 1999;79(4):1283-316.

Cao Y. Multifarious functions of PDGFs and PDGFRs in tumor growth and metastasis. Trends Mol Med. 2013;19(8):460-73.

Kang S. Two axes in platelet-derived growth factor signaling: tyrosine phosphorylation and reactive oxygen species. Cell Mol Lif Sci. 2007;64(5):533-41.

Feigelson S, Fitzer C, Eisenbach L. The role of platelet derived growth factor (PDGF) and its receptors in cancer and metastasis. Cancer Metastasis Biology and Treatment. 2006;2:167-86.

Demoulin JB, Essahir A. PDGF receptor signaling networks in normal and cancer cells. Cytokine Growth Factor Rev. 2014;25(3): 273-83.

Calvo E, Bolós V, Grande E. Multiple roles and therapeutic implications of Akt signaling in cancer. Onco Targets Ther. 2009;2:135-50.

Jurek A, Heldn, C, Lennartsson J. Platelet derived growth factor-induced signaling pathways interconnect to regulate the temporal pattern of Erk1/2 phosphorylation. Cell Signal. 2011;23(1):280-7.

Liu KW, Hu B, Cheng SY. Platelet-derived growth factor receptor alpha in glioma: a bad seed. Chin. J. Cancer. 2011;30(9):590-602.

Arrondeau J, Huillard O, Tlemsani C, Cessot A, Boudou-Rouquerre P, Blanchet B, et al. Investigational therapies up to phase II which target PDGF receptors: potential anti-cancer therapeutics. Expert Opin. Investig. Drugs. 2015;24(5):1-15.

Fabbro D. 25 years of small molecular weight kinase inhibitors: potentials and limitations. Mol. Pharmacol. 2015;87(5):766-75.

Rasheed S, Nelson W, Toth E, Arnstein P, Gardner M. Characterization of a newly derived human sarcoma cell line (HT1080). Cancer. 1974;33(4):1027-33.

Gupta Y, Grabocka E, Bar-Sagi D. RAS oncogenes: weaving a tumorigenic web. Nat. Rev. Cancer. 2011;11(11):761-74.

Gacche R, Meshram R. Angiogenic factors as potential drug target: Efficacy and limitations of anti-angiogenic therapy. Biochim Biophys Acta. 2014;1846(1):161-79.

Contreras M. Efecto de dos péptidos sintéticos sobre la función del PDGF en la vía de señalización PI3K/Akt en células tumorales humanas HT1080. Tesis maestría. 2009. Pontificia Universidad Javeriana. Facultad de Ciencias. Departamento de Nutrición y Bioquímica. Bogotá. Colombia. 147p.

Nazarenko I, Hede S, He X, Hedrén A, Thompson J, Lindström M, et al. PDGF and PDGF receptors in glioma. Ups J Med Sci. 2012;117(2):99-112.

Abouantoun T, MaCDonald T. Imatinib blocks migration and invasion of medulloblastoma cells by concurrently inhibiting activation of platelet-derived growth factor receptor and transactivation of epidermal growth factor receptor. Mol Cancer Ther. 2009;8(5):1137-47.

Nishimura Y, Bereczky B, Yoshioka K, Taniguchi, S, Itoh K. A novel role of Rho-kinase in the regulation of ligand-induced phosphorylated EGFR endocytosis via the early/late endocytic pathway in human fibrosarcoma cells. J Mol Histol. 2011;42(5):427-42.

Cao J, Shafee N, Vickery L, Kaluz S, Ru N, Stanbridge E. MEK1act/tubulin interactions is an important determinant of mitotic stability in cultured HT1080 human fibrosarcoma cells. Cancer Res. 2010;70(14):6004-14.

Ariza M. Síntesis y evaluación de la afinidad de péptidos sintéticos por el receptor del factor de crecimiento derivado de plaquetas (PDGF). Tesis de Maestría. 2007. Pontificia Universidad Javeriana. Facultad de Ciencias. Departamento de Nutrición y Bioquímica. Bogotá. Colombia. 150p.

Fthenou E, Zafiropoulos A, Tsatsakis A, Stathopoulos A, Karamanos N, Tzanakakis G. Chondroitin sulfate A chains enhance platelet derived growth factor-mediated signaling in fibrosarcoma cells. Int J Biochem Cell Biol. 2006;38(12):2141-50.

Chiara F, Bishayee S, Heldin C, Demoulin J. Autoinhibition of the platelet-derived growth factor receptor β tyrosine kinase by its C-terminal tail. J Biol Chem. 2004;279(19):19732-8.

Yamamoto M, Tova Y, Jensen R, Ishikawa Y. Caveolin is an inhibitor of platelet-derived growth factor receptor signaling. Exp Cell Res. 1999;247(2):380-8.

Brennand D, Dennehy U, Ellis V, Scully M, Tripathi P, Kakkar V, et al. Identification of a cyclic peptide inhibitor of platelet-derived growth factor-BB receptor-binding and mitogen-induced DNA synthesis in human fibroblasts. FEBS Lett. 1997;413(1):70-4.

Engström U, Engström A, Ernlund A, Westermark B, Heldin C. Identification of a peptide antagonist for platelet-derived growth factor. J Biol Chem. 1992;267(23):16581-7.

Wu J, Goswami R, Cai X, Exum S, Huang X, Zhang L, et al. Regulation of the platelet-derived growth factor receptor-beta by G protein-coupled receptor kinase-5 in vascular smooth muscle cells involves the phosphatase Shp2. J Biol Chem. 2006; 281(49):37758-72.

Welsh L. Platelet-derived growth factor receptor signals. J Biol Chem. 1994;269(51):32023-6.

Kashishian A, Kazlauskas A, Cooper J. Phosphorylation sites in the PDGF receptor with different specificities for binding GAP and PI3 kinase in vivo. EMBO J. 1992;11(4):1373-1382.

Lin H, Ballou L, Lin R. Stimulation of the αIA adrenergic receptor inhibits PDGF-induced PDGFβ receptor Tyr751 phosphorylation and PI 3-kinase activation. FEBS Lett. 2003;540(1-3):106-10.

Lin X, Takahashi K, Liu Y, Zamora P. A synthtetic, bioactive PDGF mimetic with binding to both α–PDGF y β–PDGF receptors. Growth Factors. 2007;25(2):87-93.

Dance M, Montagner A, Salles J, Yart A, Raynal P. The molecular functions of Shp2 in the Ras/Mitogen-activated protein kinase (Erk1/2) pathway. Cell Signal. 2008;20(3):453-9.

Rönnstrand L, Arvidsson A, Kallin A, Rorsman C, Hellman U, Engström U, et al. SHP-2 binds to Tyr763 and Tyr1009 in the PDGF β-receptor and mediates PDGF-induced activation of the Ras/MAP kinase pathway and chemotaxis. Oncogene. 1999;18(25):3696-02.

Nakata S, Fujita N, Kitagawa Y, Okamoto R, Ogita H, Takai Y. Regulation of platelet-derived growth factor receptor activation by afadin through Shp2. J Biol Chem. 2007;282(52):37815-25.

Lennartsson J, Burovic F, Witek B, Jurek A, Heldin C. Erk5 is necessary for sustained PDGF-induced Akt phosphorylation and inhibition of apoptosis. Cell Signal. 2010;22(6):955-60.

Gupta S, Stuffrein S, Plattner R, Tencati M, Gray C, Whang Y, et al. Role of phosphoinositide 3-kinase in the aggressive tumor growth of HT1080 human fibrosarcoma cells. Mol Cell Biol. 2001;21(17):5846-56.

Katz M, Amit I, Yarden Y. Regulation of MAPKs by growth factors and receptor tyrosine kinases. Biochim Biophys Acta. 2007;1773(8):1161-76.

McCubrey J, Steelman L, Chappell W, Abrams S, Wong E, Chang F, et al. Roles of the Raf/Mek/Erk pathway in cell growth, malignant transformation and drug resistance. Biochim Biophys Acta. 2007;1773(8):1263-84.

Pratilas C, Solit D. Targeting the mitogen-activated protein kinase pathway: physiological feedback and drug response. Clin Cancer Res. 2010;16(13):3329-34.

Hoshino R, Tanimura S, Watanabe K, Kataoka T, Kohno M. Blockade of the extracellular signal-regulated kinase pathway induces marked G1 cell cycle arrest and apoptosis in tumor cells in which the pathway is constitutively activated. J Biol Chem. 2001;276(4):2686-92.

Matsui T, Murata H, Sowa Y, Sakabe T, Koto K, Horie N, et al. A novel Mek1/2 inhibitor induces G1/s cell cycle arrest in human fibrosarcoma cells. Oncol Rep. 2010; 24(2):329-33.

Canavese M, Santo L, Raje N. Cyclin dependent kinases in cancer: Potential for therapeutic intervention. Cancer Biol Ther. 2012;13(7):451-7.

Jung S, Park S, Kim W, Moon S. Ras/ERK1 pathway regulation of p27KIP1-mediated G1-phase cell-cycle arrest in cordycepin-induced inhibition of the proliferation of vascular smooth muscle cells. Eur J Pharmacol. 2012;681(1-3):15-22.

Piscazzi A, Costantino E, Maddalena F, Natalicchio M, Gerardi A, Antonetti R, et al. Activation of the RAS/RAF/ERK signaling pathway contributes to resistance to sunitinib in thyroid carcinoma cell lines. J Clin Endocrinol Metab. 2012;97(6):1-9.

Cargnello M, Roux P. Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiol Mol Biol Rev. 2011;75(1):50-83.

Publicado
2018-05-01
Cómo citar
Grismaldo, A., & Morales, L. (2018). Moléculas moduladoras de vías de señalización basales y desencadenadas por el Factor de Crecimiento Derivado de Plaquetas (PDGF) en un modelo celular de fibrosarcoma humano. Revista De Nutrición Clínica Y Metabolismo, 1(1), 42-52. https://doi.org/10.35454/rncm.v1n1.076
Sección
Artículo original