Effect of tumor gangliosides on tyrosine phosphorylation of p125FAK in platelet adhesion to collagen

Chen,Yi-Xin; Chen,Xiao-Wen; Li,Chang-Gang; Yue,Li-Jie; Mai,Hui-Rong; Wen,Fei-Qiu

doi:10.3892/or.2012.2092

Effect of tumor gangliosides on tyrosine phosphorylation of p125FAK in platelet adhesion to collagen

Authors:
- Yi-Xin Chen
- Xiao-Wen Chen
- Chang-Gang Li
- Li-Jie Yue
- Hui-Rong Mai
- Fei-Qiu Wen
View Affiliations

Affiliations: Cancer Institute, the Second Clinical College of Medicine, Shenzhen People's Hospital, Jinan University, Shenzhen, Guangdong 51802, P.R. China, Department of Hematology and Oncology, Shenzhen Children's Hospital, Shenzhen, Guangdong 518026, P.R. China
Published online on: October 19, 2012 https://doi.org/10.3892/or.2012.2092
Pages: 343-348

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The exact mechanisms as to how platelets influence blood-borne metastasis remain poorly understood. Gangliosides, sialic acid-containing glycosphingolipids, are associated with tumor progression and metastasis in humans. Gangliosides isolated from tumor cells promote collagen-stimulated platelet aggregation and ATP secretion and enhance platelet adhesion to immobilized collagen. Gangliosides interact with a number of cell surface receptors including integrin receptors. In this study, we examined the effects of α2β1 integrin-mediated platelet adhesion to collagen and phosphotyrosine signaling of focal adhesion kinase, p125FAK (FAK). platelets pre-incubated with neuroblastoma tumor gangliosides (NBTGs) or their major component GD2 (disialoganglioside) were more adherent to immobilized collagen (OD570 0.43±0.12, 0.39±0.13) compared to platelets pre-incubated with MTB (0.14±0.06, p<0.001); the effect of NBTGs was blocked by F-17 anti-α2 antibody. Pre-incubation of platelets with NBTGs resulted in a marked increase in the phosphotyrosine content of p125FAK in the adherent platelets compared to the MTB-pre-incubated adherent platelets. F-17 anti-α2 antibody decreased protein tyrosine phosphorylation of NBTG-incubated platelets adherent to collagen. These results indicate that the tumor gangliosides enhance platelet adhesion to extracellular matrix collagen by upregulating integrin α2β1-mediated tyrosine phosphorylation of p125FAK, thereby providing insight into how this interaction may be involved in neuroblastoma metastasis.

View Figures

View References

1	Brooks SA, Lomax-Browne HJ, Carter TM, Kinch CE and Hall DM: Molecular interactions in cancer cell metastasis. Acta Histochem. 112:3–25. 2010. View Article : Google Scholar : PubMed/NCBI
2	Sahai E: Illuminating the metastatic process. Nat Rev Cancer. 7:737–749. 2007. View Article : Google Scholar : PubMed/NCBI
3	Yu RK, Tsai YT, Ariga T and Yanagisawa M: Structures, biosynthesis, and functions of gangliosides-an overview. J Oleo Sci. 60:537–544. 2011. View Article : Google Scholar : PubMed/NCBI
4	Yates AJ, Saqr HE and Van Brocklyn J: Ganglioside modulation of the PDGF receptor. A model for ganglioside functions. J Neurooncol. 24:65–73. 1995. View Article : Google Scholar : PubMed/NCBI
5	Duchemin AM, Ren Q, Mo L, Neff NH and Hadjiconstantinou M: GM1 ganglioside induces phosphorylation and activation of Trk and Erk in brain. J Neurochem. 81:696–707. 2002. View Article : Google Scholar : PubMed/NCBI
6	Garofalo T, Misasi R, Mattei V, et al: Association of the death-inducing signaling complex with microdomains after triggering through CD95/Fas. Evidence for caspase-8-ganglioside interaction in T cells. J Biol Chem. 278:8309–8315. 2003. View Article : Google Scholar : PubMed/NCBI
7	Wang XQ, Sun P and Paller AS: Ganglioside induces caveolin-1 redistribution and interaction with the epidermal growth factor receptor. J Biol Chem. 277:47028–47034. 2002. View Article : Google Scholar : PubMed/NCBI
8	Singleton DW, Lu CL, Colella R and Roisen FJ: Promotion of neurite outgrowth by protein kinase inhibitors and ganglioside GM1 in neuroblastoma cells involves MAP kinase ERK1/2. Int J Dev Neurosci. 18:797–805. 2000. View Article : Google Scholar : PubMed/NCBI
9	Valentino LA and Ladisch S: Tumor gangliosides enhance alpha2 beta1 integrin-dependent platelet activation. Biochim Biophys Acta. 1316:19–28. 1996. View Article : Google Scholar : PubMed/NCBI
10	Fang LH, Lucero M, Kazarian T, Wei Q, Luo FY and Valentino LA: Effects of neuroblastoma tumor gangliosides on platelet adhesion to collagen. Clin Exp Metastasis. 15:33–40. 1997. View Article : Google Scholar : PubMed/NCBI
11	Valentino LA and Ladisch S: Circulating tumor gangliosides enhance platelet activation. Blood. 83:2872–2877. 1994.PubMed/NCBI
12	Hakomori S and Igarashi Y: Functional role of glycosphingolipids in cell recognition and signaling. J Biochem. 118:1091–1103. 1995.PubMed/NCBI
13	Hynes RO: Integrins: bidirectional, allosteric signaling machines. Cell. 110:673–687. 2002. View Article : Google Scholar : PubMed/NCBI
14	Wang XQ, Sun P and Paller AS: Ganglioside modulation regulates epithelial cell adhesion and spreading via ganglioside-specific effects on signaling. J Biol Chem. 277:40410–40419. 2002. View Article : Google Scholar : PubMed/NCBI
15	Hildebrand JD, Schaller MD and Parsons JT: Identification of sequences required for the efficient localization of the focal adhesion kinase, pp125FAK, to cellular focal adhesions. J Cell Biol. 123:993–1005. 1993. View Article : Google Scholar : PubMed/NCBI
16	Lipfert L, Haimovich B, Schaller MD, Cobb BS, Parsons JT and Brugge JS: Integrin-dependent phosphorylation and activation of the protein tyrosine kinase pp125FAK in platelets. J Cell Biol. 119:905–912. 1992. View Article : Google Scholar : PubMed/NCBI
17	Wen FQ, Jabbar AA, Patel DA, Kazarian T and Valentino LA: Atherosclerotic aortic gangliosides enhance integrin-mediated platelet adhesion to collagen. Arterioscler Thromb Vasc Biol. 19:519–524. 1999. View Article : Google Scholar : PubMed/NCBI
18	Wu G, Lu ZH, Wei TJ, Howells RD, Christoffers K and Ledeen RW: The role of GM1 ganglioside in regulating excitatory opioid effects. Ann NY Acad Sci. 845:126–138. 1998. View Article : Google Scholar : PubMed/NCBI
19	Wiesner T, Bugl S, Mayer F, Hartmann JT and Kopp HG: Differential changes in platelet VEGF, Tsp, CXCL12, and CXCL4 in patients with metastatic cancer. Clin Exp Metastasis. 27:141–149. 2010. View Article : Google Scholar : PubMed/NCBI
20	Wang Y and Zhang H: Platelet-induced inhibition of tumor cell growth. Thromb Res. 123:324–330. 2008. View Article : Google Scholar : PubMed/NCBI
21	Zaslavsky A, Baek KH, Lynch RC, et al: Platelet-derived thrombospondin-1 is a critical negative regulator and potential biomarker of angiogenesis. Blood. 115:4605–4613. 2010. View Article : Google Scholar : PubMed/NCBI
22	Ho-Tin-Noe B, Goerge T, Cifuni SM, Duerschmied D and Wagner DD: Platelet granule secretion continuously prevents intratumor hemorrhage. Cancer Res. 68:6851–6858. 2008. View Article : Google Scholar : PubMed/NCBI
23	Kopp HG, Placke T and Salih HR: Platelet-derived transforming growth factor-beta down-regulates NKG2D thereby inhibiting natural killer cell antitumor reactivity. Cancer Res. 69:7775–7783. 2009. View Article : Google Scholar : PubMed/NCBI
24	Nieswandt B, Hafner M, Echtenacher B and Mannel DN: Lysis of tumor cells by natural killer cells in mice is impeded by platelets. Cancer Res. 59:1295–1300. 1999.PubMed/NCBI
25	Gawaz M and Geisler T: Coronary artery disease: platelet activity: an obstacle for successful PCI. Nat Rev Cardiol. 6:391–392. 2009. View Article : Google Scholar : PubMed/NCBI
26	Amirkhosravi A, Mousa SA, Amaya M, et al: Inhibition of tumor cell-induced platelet aggregation and lung metastasis by the oral GpIIb/IIIa antagonist XV454. Thromb Haemost. 90:549–554. 2003.PubMed/NCBI
27	Shield K, Riley C, Quinn MA, Rice GE, Ackland ML and Ahmed N: Alpha2beta1 integrin affects metastatic potential of ovarian carcinoma spheroids by supporting disaggregation and proteolysis. J Carcinog. 6:112007. View Article : Google Scholar : PubMed/NCBI
28	Matsuoka T, Yashiro M, Nishimura S, et al: Increased expression of α₂β₁-integrin in the peritoneal dissemination of human gastric carcinoma. Int J Mol Med. 5:21–25. 2000.
29	Clark EA and Brugge JS: Integrins and signal transduction pathways: the road taken. Science. 268:233–239. 1995. View Article : Google Scholar : PubMed/NCBI
30	Shattil SJ, Kashiwagi H and Pampori N: Integrin signaling: the platelet paradigm. Blood. 91:2645–2657. 1998.PubMed/NCBI
31	Wang XQ, Sun P and Paller AS: Inhibition of integrin-linked kinase/protein kinase B/Akt signaling: mechanism for ganglioside-induced apoptosis. J Biol Chem. 276:44504–44511. 2001. View Article : Google Scholar : PubMed/NCBI
32	Burridge K, Turner CE and Romer LH: Tyrosine phosphorylation of paxillin and pp125FAK accompanies cell adhesion to extracellular matrix: a role in cytoskeletal assembly. J Cell Biol. 119:893–903. 1992. View Article : Google Scholar : PubMed/NCBI
33	Golden A, Nemeth SP and Brugge JS: Blood platelets express high levels of the pp60c-src-specific tyrosine kinase activity. Proc Natl Acad Sci USA. 83:852–856. 1986. View Article : Google Scholar : PubMed/NCBI
34	Golden A, Brugge JS and Shattil SJ: Role of platelet membrane glycoprotein IIb-IIIa in agonist-induced tyrosine phosphorylation of platelet proteins. J Cell Biol. 111:3117–3127. 1990. View Article : Google Scholar : PubMed/NCBI
35	Haimovich B, Lipfert L, Brugge JS and Shattil SJ: Tyrosine phosphorylation and cytoskeletal reorganization in platelets are triggered by interaction of integrin receptors with their immobilized ligands. J Biol Chem. 268:15868–15877. 1993.
36	Polanowska-Grabowska R, Geanacopoulos M and Gear AR: Platelet adhesion to collagen via the alpha 2 beta 1 integrin under arterial flow conditions causes rapid tyrosine phosphorylation of pp125FAK. Biochem J. 296:543–547. 1993.PubMed/NCBI
37	Smilowitz HM, Aramli L, Xu D and Epstein PM: Phosphotyrosine phosphatase activity in human platelets. Life Sci. 49:29–37. 1991. View Article : Google Scholar : PubMed/NCBI
38	Nakamura S and Yamamura H: Thrombin and collagen induce rapid phosphorylation of a common set of cellular proteins on tyrosine in human platelets. J Biol Chem. 264:7089–7091. 1989.PubMed/NCBI
39	Gilmore AP and Burridge K: Molecular mechanisms for focal adhesion assembly through regulation of protein-protein interactions. Structure. 4:647–651. 1996. View Article : Google Scholar : PubMed/NCBI
40	Frangioni JV, Oda A, Smith M, Salzman EW and Neel BG: Calpain-catalyzed cleavage and subcellular relocation of protein phosphotyrosine phosphatase 1B (PTP-1B) in human platelets. EMBO J. 12:4843–4856. 1993.
41	Sun P, Wang XQ, Lopatka K, Bangash S and Paller AS: Ganglioside loss promotes survival primarily by activating integrin-linked kinase/Akt without phosphoinositide 3-OH kinase signaling. J Invest Dermatol. 119:107–117. 2002. View Article : Google Scholar : PubMed/NCBI
42	Meuillet E, Cremel G, Dreyfus H and Hicks D: Differential modulation of basic fibroblast and epidermal growth factor receptor activation by ganglioside GM3 in cultured retinal Muller glia. Glia. 17:206–216. 1996. View Article : Google Scholar : PubMed/NCBI
43	Zou CY, Wen FQ, Chen YX, Liu ZP and Zhang ZX: Effect of integrin alpha2beta1 on invasion and migration of neuroblastoma cells. Zhongguo Dang Dai Er Ke Za Zhi. 10:386–390. 2008.(In Chinese).
44	Jabbar AA, Kazarian T, Hakobyan N and Valentino LA: Gangliosides promote platelet adhesion and facilitate neuroblastoma cell adhesion under dynamic conditions simulating blood flow. Pediatr Blood Cancer. 46:292–299. 2006. View Article : Google Scholar : PubMed/NCBI