Molecular mechanisms regulating metastasis of cancer cells with special emphasis on rhabdomyosarcoma
Maciej Tarnowski 1 , Katarzyna Grymuła 1 , Marta Tkacz 1 , Michał Czerewaty 1 , Agata Poniewierska-Baran 1 , Mariusz Zdzisław Ratajczak 1Abstract
Rhabdomyosarcoma (RMS) is a malignant tumor of soft tissue derived from embryonic mesenchymal and/or neuroectodermal tissues. It is most often associated with other genetic syndromes such as Li-Fraumeni or Bechwith-Wiedeman. RMS cells show morphological similarities to striated muscle and the presence of specific markers of muscle tissue. At the histological level, it is divided into two subtypes (alveolar RMS – ARMS and embryonal RMS – ERMS), which differ in their genetic background, and prognosis. In recent years there has been significant progress in understanding the mechanisms that regulate RMS cell growth and metastasis. Recently, a number of several chemokines, cytokines or growth factors and their receptors were identified involved in RMS pathogenesis as well as animal models of this tumor have been developed. This knowledge is of great importance in the development of potential therapeutic strategies not only in RMS, but also other types of cancer. This paper will discuss the theories of the origin of this rare tumor and the molecular mechanisms involved in its growth and metastasis. The processes and mechanisms described herein, such as chemotaxis, adhesion, proliferation, intracellular signal transduction, seem to universal for number of cancer types.
References
- 1. Amin M.A., Volpert O.V., Woods J.M., Kumar P., Harlow L.A., KochA.E.: Migration inhibitory factor mediates angiogenesis via mitogen-activatedprotein kinase and phosphatidylinositol kinase. Circ.Res., 2003; 93: 321-329
Google Scholar - 2. Anderson J., Gordon A., Pritchard-Jones K., Shipley J.: Genes,chromosomes, and rhabdomyosarcoma. Genes Chromosomes Cancer,1999; 26: 275-285
Google Scholar - 3. Arcuri F., Cintorino M., Carducci A., Papa S., Riparbelli M.G., MangioniS., Di Blasio A.M., Tosi P., Viganò P.: Human decidual naturalkiller cells as a source and target of macrophage migration inhibitoryfactor. Reproduction, 2006; 131: 175-182
Google Scholar - 4. Baron N., Deuster O., Noelker C., Stüer C., Strik H., Schaller C.,Dodel R., Meyer B., Bacher M.: Role of macrophage migration inhibitoryfactor in primary glioblastoma multiforme cells. J. Neurosci.Res., 2011; 89: 711-717
Google Scholar - 5. Barr F.G.: Gene fusions involving PAX and FOX family members inalveolar rhabdomyosarcoma. Oncogene, 2001; 20: 5736-5746
Google Scholar - 6. Barr F.G.: Molecular genetics and pathogenesis of rhabdomyosarcoma.J. Pediatr. Hematol. Oncol., 1997; 19: 483-491
Google Scholar - 7. Barr F.G., Nauta L.E., Davis R.J., Schafer B.W., Nycum L.M., BiegelJ.A.: In vivo amplification of the PAX3-FKHR and PAX7-FKHR fusiongenes in alveolar rhabdomyosarcoma. Hum. Mol. Genet., 1996; 5:15-21
Google Scholar - 8. Battegay E.J.: Angiogenesis: mechanistic insights, neovasculardiseases, and therapeutic prospects. J. Mol. Med. (Berl)., 1995; 73:333-346
Google Scholar - 9. Bellamy W.T.: Expression of vascular endothelial growth factorand its receptors in multiple myeloma and other hematopoieticmalignancies. Semin. Oncol., 2001; 28: 551-559
Google Scholar - 10. Bender J.G., Yamashiro D.J., Fox E.: Clinical development of VEGFsignaling pathway inhibitors in childhood solid tumors. Oncologist,2011; 16: 1614-1625
Google Scholar - 11. Bennicelli J.L., Advani S., Schäfer B.W., Barr F.G.: PAX3 and PAX7exhibit conserved cis-acting transcription repression domains andutilize a common gain of function mechanism in alveolar rhabdomyosarcoma.Oncogene, 1999; 18: 4348-4356
Google Scholar - 12. Bernhagen J., Krohn R., Lue H., Gregory J.L., Zernecke A., KoenenR.R., Dewor M., Georgiev I., Schober A., Leng L., Kooistra T.,Fingerle-Rowson G., Ghezzi P., Kleemann R., McColl S.R., Bucala R.,Hickey M.J., Weber C.: MIF is a noncognate ligand of CXC chemokinereceptors in inflammatory and atherogenic cell recruitment. Nat.Med., 2007; 13: 587-596
Google Scholar - 13. Bourboulia D., Stetler-Stevenson W.G.: Matrix metalloProteinases(MMPs) and tissue inhibitors of metalloproteinases (TIMPs): positiveand negative regulators intumor cell adhesion. Semin. CancerBiol., 2010; 20: 161-168
Google Scholar - 14. Burns J.M., Summers B.C., Wang Y., Melikian A., Berahovich R.,Miao Z., Penfold M.E., Sunshine M.J., Littman D.R., Kuo C.J., Wei K.,McMaster B.E., Wright K., Howard M.C., Schall T.J.: A novel chemokinereceptor for SDF-1 and I-TAC involved in cell survival, cell adhesion,and tumor development. J. Exp. Med., 2006; 203: 2201-2213
Google Scholar - 15. Carmeliet P.: Mechanisms of angiogenesis and arteriogenesis.Nat. Med., 2000; 6: 389-395
Google Scholar - 16. Caspary T., Cleary M.A., Perlman E.J., Zhang P., Elledge S.J., TilghmanS.M.: Oppositely imprinted genes p57Kip2 and Igf2 interact ina mouse model for Beckwith–Wiedemann syndrome. Genes Dev.,1997; 13: 3115-3124
Google Scholar - 17. Cavenee W.K.: Muscling in on rhabdomyosarcoma. Nat. Med.,2002; 8: 1200-1201
Google Scholar - 18. Chesney J., Metz C., Bacher M., Peng T., Meinhardt A., BucalaR.: An essential role for macrophage migration inhibitory factor(MIF) in angiogenesis and the growth of a murine lymphoma. Mol.Med., 1999; 5: 181-191
Google Scholar - 19. Cirri P., Chiarugi P.: Cancer associated fibroblasts: the dark sideof the coin. Am. J. Cancer Res., 2011; 1: 482-497
Google Scholar - 20. Comoglio P.M., Trusolino L.: Invasive growth: from developmentto metastasis. J. Clin. Invest., 2002; 109: 857-862
Google Scholar - 21. Cournia Z., Leng L., Gandavadi S., Du X., Bucala R, JorgensenW.L.: Discovery of human macrophage migration inhibitory factor(MIF)-CD74 antagonists via virtual screening. J. Med. Chem., 2009;52: 416-424
Google Scholar - 22. Dagher R., Helman L.: Rhabdomyosarcoma: an overview. Oncologist,1999; 4: 34-44
Google Scholar - 23. Diller L., Sexsmith E., Gottlieb A., Li F.P., Malkin D.: Germline p53mutations are frequently detected in young children with rhabdomyosarcoma.J. Clin. Invest., 1995; 95: 1606-1611
Google Scholar - 24. Diomedi-Camassei F., McDowell H.P., De Ioris M.A., Uccini S., AltavistaP., Raschellà G., Vitali R., Mannarino O., De Sio L., Cozzi D.A.,Donfrancesco A., Inserra A., Callea F., Dominici C.: Clinical significanceof CXC chemokine receptor-4 and c-Met in childhood rhabdomyosarcoma.Clin. Cancer Res., 2008; 14: 4119-4127
Google Scholar - 25. Drake N.M., DeVito L.M., Cleland T.A., Soloway P.D.: ImprintedRasgrf1 expression in neonatal mice affects olfactory learning andmemory. Genes Brain Behav., 2011; 10: 392-403
Google Scholar - 26. Dvorak H.F.: VPF/VEGF and the angiogenic response. Semin.Perinatol., 2000; 24: 75-78
Google Scholar - 27. El-Attar H.A., Sheta M.I.: Hepatocyte growth factor profile withbreast cancer. Indian J. Pathol. Microbiol., 2011; 54: 509-513
Google Scholar - 28. El-Houseini M.E., Abdel-Azim S.A., El-Desouky G.I., Abdel-HadyS., El-Hamad M.F., Kamel A.M.: Clinical significance of vascularendothelial growth factor (VEGF) in sera of patients with pediatricmalignancies. J. Egypt. Natl. Canc. Inst., 2004; 16: 57-61
Google Scholar - 29. Fernández-Medarde A., Santos E.: Ras in cancer and developmentaldiseases. Genes Cancer, 2011; 2: 344-358
Google Scholar - 30. Folkman J.: Angiogenesis in cancer, vascular, rheumatoid andother disease. Nat. Med., 1995; 1: 27-31
Google Scholar - 31. Folkman J.: Angiogenesis. Annu. Rev. Med., 2006; 57: 1-18
Google Scholar - 32. Folkman J.: Role of angiogenesis in tumor growth and metastasis.Semin. Oncol., 2002; 29: 15-18
Google Scholar - 33. Frascella E., Toffolatti L., Rosolen A.: Normal and rearrangedPAX3 expression in human rhabdomyosarcoma. Cancer Genet. Cytogenet.,1998; 102: 104-109
Google Scholar - 34. Fredericks W.J., Ayyanathan K., Herlyn M., Friedman J.R., RauscherF.J. 3rd: An engineered PAX3-KRAB transcriptional repressorinhibits the malignant phenotype of alveolar rhabdomyosarcomacells harboring the endogenous PAX3-FKHR oncogene. Mol. Cell.Biol., 2000; 20: 5019-5031
Google Scholar - 35. Galili N., Davis R.J., Fredericks W.J., Mukhopadhyay S., RauscherF.L. 3rd, Emanual B.S, Rovera G., Barr F.G.: Fusion of a fork head domaingene to PAX3 in the solid tumour alveolar rhabdomyosarcoma.Nat. Genet., 1993; 5: 230-235
Google Scholar - 36. Gallagher E.J., LeRoith D.: The proliferating role of insulin andinsulin-like growth factors in cancer. Trends Endocrinol. Metab.,2010; 21: 610-618
Google Scholar - 37. Gee M.F., Tsuchida R., Eichler-Jonsson C., Das B., Baruchel S.,Malkin D.: Vascular endothelial growth factor acts in an autocrinemanner in rhabdomyosarcoma cell lines and can be inhibited withall-trans-retinoic acid. Oncogene, 2005; 24: 8025-8037
Google Scholar - 38. Gerber H.P., Kowalski J., Sherman D., Eberhard D.A., FerraraN.: Complete inhibition of rhabdomyosarcoma xenograftgrowth and neovascularization requires blockade of both tumorand host vascular endothelial growth factor. Cancer Res., 2000;60: 6253-6258
Google Scholar - 39. Giavazzi R., Foppolo M., Dossi R., Remuzzi A.: Rolling and adhesionof human tumor cells on vascular endothelium under physiologicalflow conditions. J. Clin. Invest., 1993; 92: 3038-3044
Google Scholar - 40. Giordano F.J.: Angiogenesis: mechanisms, modulation, and targetedimaging. J. Nucl. Cardiol., 1999; 6: 664-671
Google Scholar - 41. Goldstein M., Meller I., Issakov J., Orr-Urtreger A.: Novel genesimplicated in embryonal, alveolar, and pleomorphic rhabdomyosarcoma:a cytogenetic and molecular analysis of primary tumors.Neoplasia, 2006; 8: 332-343
Google Scholar - 42. Goode E.L., Chenevix-Trench G., Hartmann L.C., Fridley B.L.,Kalli K.R., Vierkant R.A., Larson M.C., White K.L., Keeney G.L., ObergT.N., Cunningham J.M., Beesley J., Johnatty S.E., Chen X., GoodmanK.E. i wsp.: Assessment of hepatocyte growth factor in ovariancancer mortality. Cancer Epidemiol. Biomarkers Prev., 2011;20: 1638-1648
Google Scholar - 43. Grimstad I.A.: Direct evidence that cancer cell locomotion contributesimportantly to invasion. Exp. Cell. Res., 1987; 173: 515-523
Google Scholar - 44. Grymula K., Tarnowski M., Wysoczynski M., Drukala J., Barr F.G.,Ratajczak J., Kucia M., Ratajczak M.Z.: Overlapping and distinct roleof CXCR7-SDF-1/ITAC and CXCR4-SDF-1 axes in regulating metastaticbehavior of human rhabdomyosarcomas. Int. J. Cancer, 2010;127: 2554-2568
Google Scholar - 45. Gurney J.G., Severson R.K., Davis S., Robison L.L.: Incidence ofcancer in children in the United States. Sex-, race-, and 1-year age–specific rates by histologic type. Cancer, 1995; 75: 2186-2195
Google Scholar - 46. Gutkind J.S.: The pathways connecting G protein-coupled receptorsto the nucleus through divergent mitogen-activated proteinkinase cascades. J. Biol. Chem., 1998; 273: 1839-1842
Google Scholar - 47. Hagemann T., Wilson J., Kulbe H., Li N.F., Leinster D.A., CharlesK., Klemm F., Pukrop T., Binder C., Balkwill F.R.: Macrophages induceinvasiveness of epithelial cancer cells via NF-kappa B and JNK. J.Immunol., 2005; 175: 1197-1205
Google Scholar - 48. Harrison C.: G protein-coupled receptors: insights into chemokinereceptors. Nat. Rev. Drug. Discov., 2010; 9: 920
Google Scholar - 49. Hellevik T., Pettersen I., Berg V., Winberg J.O., Moe B.T., BartnesK., Paulssen R.H., Busund L.T., Bremnes R., Chalmers A., Martinez-ZubiaurreI.: Cancer-associated fibroblasts from human NSCLC surviveablative doses of radiation but their invasive capacity is reduced.Radiat. Oncol., 2012; 7: 59
Google Scholar - 50. Hida K., Kawamoto T., Ohga N., Akiyama K., Hida Y., ShindohM.: Altered angiogenesis in the tumor microenvironment. Pathol.Int., 2011; 61: 630-637
Google Scholar - 51. Houghton P.J., Morton C.L., Gorlick R., Kolb E.A., Keir S.T., ReynoldsC.P., Kang M.H., Maris J.M., Wu J., Smith M.A.: Initial testingof a monoclonal antibody (IMC-A12) against IGF-1R by the pediatricpreclinical testing program. Pediatr Blood Cancer, 2010; 54: 921-926
Google Scholar - 52. Iolascon A., Faienza M.F., Coppola B., Rosolen A., Basso G., DellaRagione F., Schettini F.: Analysis of cyclin-dependent kinase inhibitorgenes (CDKN2A, CDKN2B, and CDKN2C) in childhood rhabdomyosarcoma.Genes Chromosomes Cancer, 1996; 15: 217-222
Google Scholar - 53. Jakubczak J.L., LaRochelle W.J., Merlino G.: NK1, a natural splicevariant of hepatocyte growth factor/scatter factor, is a partial agonistin vivo. Mol. Cell Biol., 1998; 18: 1275-1283
Google Scholar - 54. Jankowski K., Kucia M., Wysoczynski M., Reca R., Zhao D., TrzynaE., Trent J., Peiper S., Zembala M., Ratajczak J., Houghton P., Janowska-WieczorekA., Ratajczak M.Z.: Both hepatocyte growth factor(HGF) and stromal-derived factor-1 regulate the metastatic behaviorof human rhabdomyosarcoma cells, but only HGF enhances theirresistance to radiochemotherapy. Cancer Res., 2003; 63: 7926-7935
Google Scholar - 55. Jeffers M., Rong S., Vande Woude G.F.: Enhanced tumorigenicityand invasion-metastasis by hepatocyte growth factor/scatter factor–met signalling in human cells concomitant with induction of theurokinase proteolysis network. Mol. Cell Biol., 1996; 16: 1115-1125
Google Scholar - 56. Juczewska M., Chyczewska E., Naumnik W., Chyczewski L., NiklińskaW., Rogalewska A., Kovalchuk O., Nikliński J.: Endothelialcells and angiogenesis intensity in lung cancer. Folia Histochem.Cytobiol., 2001; 39: 253-258
Google Scholar - 57. Keller C., Arenkiel B.R., Coffin C.M., El-Bardeesy N., DePinho R.A.,Capecchi M.R.: Alveolar rhabdomyosarcomas in conditional PAX3:Fkhrmice: cooperativity of Ink4a/ARF and Trp53 loose of funcktion.Genes Dev., 2004; 18: 2614-2626
Google Scholar - 58. Khan J., Simon R., Bittner M., Chen Y., Leighton S.B., PohidaT., Smith P.D., Jiang Y., Gooden G.C., Trent J.M., Meltzer P.S.: Geneexpression profiling of alveolar rhabdomyosarcoma with cDNA microarrays.Cancer Res., 1998; 58: 5009-5013
Google Scholar - 59. Knudsen E.S., Pazzagli C., Born T.L., Bertolaet B.L., Knudsen K.E.,Arden K.C., Henry R.R, Feramisco J.R.: Elevated cyclins and cyclin–dependent kinase activity in the rhabdomyosarcoma cell line RD.Cancer Res., 1998; 58: 2042-2049
Google Scholar - 60. Leng L., Metz C.N., Fang Y., Xu J., Donnelly S., Baugh J., DeloheryT., Chen Y., Mitchell R.A., Bucala R.: MIF signal transduction initiatedby binding to CD74. J. Exp. Med., 2003; 197: 1467-1476
Google Scholar - 61. Libura J., Drukala J., Majka M., Tomescu O., Navenot J.M., KuciaM., Marquez L., Peiper S.C, Barr F.G., Janowska-Wieczorek A., RatajczakM.Z.: CXCR4-SDF-1 signaling is active in rhabdomyosarcoma cells and regulates locomotion, chemotaxis, and adhesion. Blood,2002; 100: 2597-2606
Google Scholar - 62. Lukasiewicz E., Miekus K., Kijowski J., Drabik G., Wilusz M., Bobis-WozowiczS., Majka M.: Inhibition of rhabdomyosarcoma’s metastaticbehavior through downregulation of MET receptor signaling.Folia Histochem. Cytobiol., 2009; 47: 485-489
Google Scholar - 63. Lynch C.A., Tycko B., Bestor T.H., Walsh C.P.: Reactivation of a silencedH19 gene in human rhabdomyosarcoma by demethylationof DNA but not by histone hyperacetylation. Mol. Cancer, 2002; 1: 2
Google Scholar - 64. Maher E.R., Reik W.: The two-domain hypothesis in Beckwith–Wiedemann syndrome. J. Clin. Invest., 2000;106: 739-740
Google Scholar - 65. Maksym R.B., Tarnowski M., Grymula K., Tarnowska J., WysoczynskiM., Liu R., Czerny B., Ratajczak J., Kucia M., Ratajczak M.Z.:The role of stromal-derived factor-1–CXCR7 axis in developmentand cancer. Eur. J. Pharmacol., 2009; 625: 31-40
Google Scholar - 66. Malkin D., Chilton-MacNeill S., Meister L.A., Sexsmith E., DillerL., Garcea R.L.: Tissue-specific expression of SV40 in tumors associatedwith the Li-Fraumeni syndrome. Oncogene, 2001; 20: 4441-4449
Google Scholar - 67. Mareel M.M., Van Roy F.M., Bracke M.E.: How and when do tumorcells metastasize? Crit. Rev. Oncol., 1993; 4: 559-594
Google Scholar - 68. Martins A.S., Olmos D., Missiaglia E., Shipley J.: Targeting theinsulin-like growth factor pathway in rhabdomyosarcomas: rationaleand future perspectives. Sarcoma, 2011; ID 209736
Google Scholar - 69. Mauro A., Ciccarelli C., De Cesaris P., Scoglio A., Bouché M., MolinaroM., Aquino A., Zani B.M.: PKCalpha-mediated ERK, JNK andp38 activation regulates the myogenic program in human rhabdomyosarcomacells. J. Cell Sci., 2002; 115: 3587-3599
Google Scholar - 70. McDowell H.P.: Update on childhood rhabdomyosarcoma. Arch.Dis. Child., 2003; 88: 354-357
Google Scholar - 71. McMahon G.: VEGF receptor signaling in tumor angiogenesis.Oncologist, 2000; 5, Suppl. 1: 3-10
Google Scholar - 72. Mendoza L., Valcárcel M., Carrascal T., Egilegor E., Salado C., SimB.K., Vidal-Vanaclocha F.: Inhibition of cytokine-induced microvasculararrest of tumor cells by recombinant endostatin preventsexperimental hepatic melanoma metastasis. Cancer Res., 2004; 64:304-310
Google Scholar - 73. Merlino G., Helman L.J.: Rhabdomyosarcoma – working out thepathways. Oncogene, 1999; 18: 5340-5348
Google Scholar - 74. Miekus K., Lukasiewicz E., Jarocha D., Sekula M., Drabik G., MajkaM.: The decreased metastatic potential of rhabdomyosarcoma cellsobtained through MET receptor downregulation and the inductionof differentation. Cell Death Dis., 2013; 4: e459
Google Scholar - 75. Myers A.L., Williams R.F., Ng C.Y., Hartwich J.E., Davidoff A.M.:Bevacizumab-induced tumor vessel remodeling in rhabdomyosarcomaxenografts increases the effectiveness of adjuvant ionizingradiation. J. Pediatr. Surg., 2010; 45: 1080-1085
Google Scholar - 76. Newton W.A. Jr., Soule E.H., Hamoudi A.B., Reiman H.M., ShimadaH., Beltangady M., Maurer H.: Histopathology of childhood sarcomas,Intergroup Rhabdomyosarcoma Studies I and II: clinicopathologiccorrelation. J. Clin. Oncol., 1988; 6: 67-75
Google Scholar - 77. Onisto M., Slongo M.I., Gregnanin L., Gastaldi T., Carli M., RosolenA.: Expression and activity of vascular endothelial growth factor andmetalloproteinases in alveolar and embryonal rhabdomyosarcomacell lines. Int. J. Oncol., 2005; 27: 791-798
Google Scholar - 78. Orimo A, Gupta P.B., Sqroi D.C., Arenzana-Seisdedos F., DelaunayT., Naeem R., Carey V.J., Richardson A.L., Weinberg R.A.: Stromalfibroblasts present in invasive human breast carcinomas promotetumor growth and angiogenesis through elevated SDF-1/CXCL12secretion. Cell, 2005; 121: 335-348
Google Scholar - 79. Ostrovsky O., Bengal E., Aronheim A.: Induction of terminal differentiationby the c-Jun dimerization protein JDP2 in C2 myoblastsand rhabdomyosarcoma cells. J. Biol. Chem., 2002; 277: 40043-40054
Google Scholar - 80. Ratajczak M.Z., Kucia M., Liu R., Shin D.M., Bryndza E., MasternakM.M., Tarnowski M., Ratajczak J., Bartke A.: RasGrf1: genomicimprinting, VSELs, and aging. Aging, 2011; 3: 692-697
Google Scholar - 81. Ratajczak M.Z., Majka M., Kucia M., Drukala J., Pietrzkowski Z.,Peiper S., Janowska-Wieczorek A.: Expression of functional CXCR4by muscle satellite cells and secretion of SDF-1 by muscle-derivedfibroblasts is associated with the presence of both muscle progenitorsin bone marrow and hematopoietic stem/progenitor cells inmuscles. Stem Cells, 2003; 21: 363-371
Google Scholar - 82. Ratajczak M.Z., Shin D.M., Kucia M.: Very small embryonic/epiblast-likestem cells a missing link to support the germ line hypothesisof cancer development? Am. J. Pathol., 2009; 174: 1985-1992
Google Scholar - 83. Rees H., Williamson D., Papanastasiou A., Jina N., Nabarro S.,Shipley J., Anderson J.: The MET receptor tyrosine kinase contributesto invasive tumor growth in rhabdomyosarcomas. GrowthFactors, 2006; 24: 197-208
Google Scholar - 84. Ren Y.X., Finckenstein F.G., Abdueva D.A., Shahbazian V., ChungB., Weinberg K.I., Triche T.J., Shimada H., Anderson M.J.: Mousemesenchymal stem cells expressing PAX-FKHR form alveolar rhabdomyosarcomasby cooperating with secondary mutations. CancerRes., 2008; 68: 6587-6597
Google Scholar - 85. Rendon B.E., Roger T., Teneng I., Zhao M., Al-Abed Y., CalandraT., Mitchell R.A.: Regulation of human lung adenocarcinoma cellmigration and invasion by macrophage migration inhibitory factor.J. Biol. Chem., 2007; 282: 29910-29918
Google Scholar - 86. Rundhaug J.E.: Matrix metalloproteinases and angiogenesis. J.Cell Mol. Med., 2005; 9: 267-285
Google Scholar - 87. Salgado R., Benoy I., Bogers J., Weytjens R., Vermeulen P., DirixL., Van Marck E.: Platelets and vascular endothelial growth factor(VEGF): a morphological and functional study. Angiogenesis, 2001;4: 37-43
Google Scholar - 88. Schwartz V., Lue H., Kraemer S., Korbiel J., Krohn R., Ohl K., BucalaR., Weber C., Bernhagen J.: A functional heteromeric MIF receptorformed by CD74 and CXCR4. FEBS Lett., 2009; 583: 2749-2757
Google Scholar - 89. Schweigerer L., Neufeld G., Mergia A., Abraham J.A., Fiddes J.C.,Gospodarowicz D.: Basic fibroblast growth factor in human rhabdomyosarcomacells: implications for the proliferation and neovascularizationof myoblast-derived tumors. Proc. Natl. Acad. Sci. USA,1987; 84: 842-846
Google Scholar - 90. Scrable H., Witte D., Shimada H., Seemayer T., Sheng W.W., SoukupS., Koufos A., Houghton P., Lampkin B., Cavenee W.: Moleculardifferential pathology of rhabdomyosarcoma. Genes ChromosomesCancer, 1989; 1: 23-35
Google Scholar - 91. Sharp R., Recio J.A, Jhappan C., Otsuka T., Liu S., Yu Y., Liu W.,Anver M., Navid F., Helman L.J., DePinho R.A., Merlino G.: Synergismbetween INK4a/ARF inactivation and aberrant HGF/SF signaling inrhabdomyosarcomagenesis. Nat. Med., 2002; 8: 1276-1280
Google Scholar - 92. Shi X., Leng L., Wang T., Wang W., Du X., Li J., McDonald C., ChenZ., Murphy J.W., Lolis E., Noble P., Knudson W., Bucala R.: CD44 is thesignaling component of the macrophage migration inhibitory factor–CD74 receptor complex. Immunity, 2006; 25: 595-606
Google Scholar - 93. Shimizu T., Abe R., Nakamura H., Ohkawara A., Suzuki M., NishihiraJ.: High expression of macrophage migration inhibitory factorin human melanoma cells and its role in tumor cell growth and angiogenesis.Biochem. Biophys. Res. Commun., 1999; 2; 264: 751-758
Google Scholar - 94. Shukla N., Ameur N., Yilmaz I., Nafa K., Lau C.Y., Marchetti A.,Borsu L., Barr F.G., Ladanyi M.: Oncogene mutation profiling of pediatricsolid tumors reveals significant subsets of embryonal rhabdomyosarcomaand neuroblastoma with mutated genes in growthsignaling pathways. Clin. Cancer Res., 2012; 18: 748-757
Google Scholar - 95. Slominski A., Wortsman J., Carlson A., Mihm M., Nickoloff B.,McClatchey K.: Molecular pathology of soft tissue and bone tumors.A review. Arch. Pathol. Lab. Med., 1999; 123: 1246-1259
Google Scholar - 96. Spaeth E.L., Dembinski J.L., Sasser A.K., Watson K., Klopp A.,Hall B., Andreeff M., Marini F.: Mesenchymal stem cell transition totumor-associated fibroblasts contributes to fibrovascular networkexpansion and tumor progression. PLoS One, 2009; 4: e4992
Google Scholar - 97. Spangenburg E.E., Booth F.W.: Multiple signaling pathways mediateLIF-induced skeletal muscle satellite cell proliferation. Am. J.Physiol. Cell Physiol., 2002; 283: C204-C211
Google Scholar - 98. Tarnowski M., Grymula K., Liu R., Tarnowska J., Drukala J., RatajczakJ., Mitchell R.A., Ratajczak M.Z., Kucia M.: Human rhabdomyosarcomassecrete mif that modulates metastatic behavior of tumorcells and inhibits recruitment of cancer associated fibroblasts. Mol.Cancer Res., 2010: 8: 1328-1343
Google Scholar - 99. Tarnowski M., Grymula K., Reca R., Jankowski K., Maksym R., TarnowskaJ., Przybylski G., Barr F.G., Kucia M., Ratajczak M.Z.: Regulationof expression of stromal-derived factor-1 receptors: CXCR4 andCXCR7 in human rhabdomyosarcomas. Mol. Cancer Res., 2010; 8: 1-14
Google Scholar - 100. Tarnowski M., Liu R., Wysoczynski M., Ratajczak J., Kucia M.,Ratajczak M.Z.: CXCR7: a new SDF-1-binding receptor in contrast tonormal CD34(+) progenitors is functional and is expressed at higherlevel in human malignant hematopoietic cells. Eur. J. Haematol.,2010; 85: 472-483
Google Scholar - 101. Tarnowski M., Schneider G., Amann G., Clark G., Houghton P.,Barr F.G., Kenner L., Ratajczak M.Z., Kucia M.: RasGRF1 regulatesproliferation and metastatic behavior of human alveolar rhabdomyosarcomas.Int. J. Oncol., 2012; 41: 995-1004
Google Scholar - 102. Taulli R., Scuoppo C., Bersani F., Accornero P., Forni P.E., MirettiS., Grinza A., Allegra P., Schmitt-Ney M., Crepaldi T., Ponzetto C.:Validation of met as a therapeutic target in alveolar and embryonalrhabdomyosarcoma. Cancer Res., 2006; 66: 4742-4749
Google Scholar - 103. Tchou J., Kossenkov A.V., Chang L., Satija C., Herlyn M., ShoweL.C., Puré E.: Human breast cancer associated fibroblasts exhibitsubtype specific gene expression profiles. BMC Med Genomics,2012; 5: 39
Google Scholar - 104. van der Voort R., Taher T.E., Derksen P.W., Spaargaren M., vander Neut R., Pals S.T.: The hepatocyte growth factor/Met pathway indevelopment, tumorigenesis, and B-cell differentiation. Adv. CancerRes., 2000; 79: 39-90
Google Scholar - 105. Veikkola T., Karkkainen M., Claesson-Welsh L., Alitalo K.: Regulationof angiogenesis via vascular endothelial growth factor receptors.Cancer Res., 2000; 60: 203-212
Google Scholar - 106. Verjans E., Noetzel E., Bektas N., Schütz A.K., Lue H., LennartzB., Hartmann A., Dahl E., Bernhagen J.: Dual role of macrophage migrationinhibitory factor (MIF) in human breast cancer. BMC Cancer,2009; 9: 230
Google Scholar - 107. Wan X., Shen N., Mendoza A., Khanna C., Helman L.J.: CCI-779inhibits rhabdomyosarcoma xenograft growth by an antiangiogenicmechanism linked to the targeting of mTOR/Hif-1α/VEGF signaling.Neoplasia, 2006; 8: 394-401
Google Scholar - 108. Wang E.S., Teruya-Feldstein J., Wu Y., Zhu Z., Hicklin D.J., MooreM.A.: Targeting autocrine and paracrine VEGF receptor pathwaysinhibits human lymphoma xenografts in vivo. Blood, 2004;104: 2893-2902
Google Scholar - 109. Wang W., Kumar P., Epstein J., Helman L., Moore J.V., Kumar S.:Insulin-like growth factor II and PAX3-FKHR cooperate in the oncogenesisof rhabdomyosarcoma. Cancer Res., 1998; 58: 4426-4433
Google Scholar - 110. Weiss L., Orr F.W., Honn K.V.: Interactions between cancer cellsand the microvasculature: a rate-regulator for metastasis. Clin. Exp.Metastasis, 1989; 7: 127-167
Google Scholar - 111. Werther K., Christensen I.J., Nielsen H.J.: Determination of vascularendothelial growth factor (VEGF) in circulating blood: significanceof VEGF in various leucocytes and platelets. Scand. J. Clin.Lab. Invest., 2002; 62: 343-350
Google Scholar - 112. Wysoczynski M., Miekus K., Jankowski K., Wanzeck J., BartoloneS., Janowska-Wieczorek A., Ratajczak J., Ratajczak M.Z.: Leukemiainhibitory factor: a newly identified metastatic factor in rhabdomyosarcomas.Cancer Res., 2007; 67: 2131-2140
Google Scholar - 113. Wysoczynski M., Shin D.M., Kucia M., Ratajczak M.Z.: Selectiveupregulation of interleukin-8 by human rhabdomyosarcomas inresponse to hypoxia: therapeutic implications. Int. J. Cancer, 2010;126: 371-381
Google Scholar - 114. Zhang L., Kashanchi F., Zhan Q. ZhanS., Brady J.N., Fornace A.J.,Seth P., Helman L.J.: Regulation of insulin-like growth factor II P3promotor by p53: a potential mechanism for tumorigenesis. CancerRes., 1996; 56: 1367-1373
Google Scholar - 115. Zlotnik A., Yoshie O.: Chemokines: a new classification sy
Google Scholar