Cancer Causes & Control

, Volume 20, Issue 10, pp 1783–1798 | Cite as

Involvement of the IGF system in fetal growth and childhood cancer: an overview of potential mechanisms

Review article

Abstract

Fetal growth is determined by a complex interplay of genetic, nutritional, environmental, and hormonal factors. Greater than expected fetal growth has been positively associated with the risk of the development of some cancers in childhood, particularly acute lymphoblastic leukemia, and the biological mechanisms underlying such associations are thought to involve insulin-like growth factors (IGFs). Circulating IGF levels are highly correlated with fetal growth, and IGFs are believed to play an important role in carcinogenesis; however, these two bodies of evidence have not been well integrated and, as a result, the potential underlying biological mechanisms linking the IGF system with the development of specific childhood cancers have not been elucidated. This review aims to draw together and summarize the literature linking the IGF system, rapidity of fetal growth, and risk of some specific childhood cancers; suggest explanations for some of the inconsistencies observed in previous studies of these associations; and propose an integrated framework for the putative involvement of the IGF system in the development of at least some childhood cancers. If the challenges involved in studying the complex IGF system can be overcome, this field presents an exciting opportunity to elucidate etiological pathways to childhood malignancies.

Keywords

Molecular epidemiology Insulin-like growth factors Cancer 

References

  1. 1.
    Caughey RW, Michels KB (2009) Birth weight and childhood leukemia: a meta-analysis and review of the current evidence. Int J Cancer 124:2658–2670PubMedGoogle Scholar
  2. 2.
    Blair E, Liu X, de Klerk N, Lawrence D (2005) Optimal fetal growth for the Caucasian singleton and assessment of appropriateness of fetal growth: an analysis of a total population perinatal database. BMC Pediatr 5:13PubMedGoogle Scholar
  3. 3.
    Milne E, Laurvick CL, Blair E, Bower C, de Klerk N (2007) Fetal growth and acute childhood leukemia: looking beyond birth weight. Am J Epidemiol 166:151–159PubMedGoogle Scholar
  4. 4.
    Milne E, Laurvick CL, Blair E, de Klerk N, Charles AK, Bower C (2008) Fetal growth and the risk of childhood CNS tumors and lymphomas in Western Australia. Int J Cancer 123:436–443PubMedGoogle Scholar
  5. 5.
    Laurvick CL, Milne E, Blair E, de Klerk N, Charles AK, Bower C (2008) Fetal growth and the risk of childhood non-CNS solid tumours in Western Australia. Br J Cancer 99:179–181PubMedGoogle Scholar
  6. 6.
    Boyne MS, Thame M, Bennett FI, Osmond C, Miell JP, Forrester TE (2003) The relationship among circulating insulin-like growth factor (IGF)-I, IGF-binding proteins-1 and -2, and birth anthropometry: a prospective study. J Clin Endocrinol Metab 88:1687–1691PubMedGoogle Scholar
  7. 7.
    Ross JA, Perentesis JP, Robison LL, Davies SM (1996) Big babies and infant leukemia: a role for insulin-like growth factor-1? Cancer Causes Control 7:553–559PubMedGoogle Scholar
  8. 8.
    Murphy VE, Smith R, Giles WB, Clifton VL (2006) Endocrine regulation of human fetal growth: the role of the mother, placenta, and fetus. Endocr Rev 27:141–169PubMedGoogle Scholar
  9. 9.
    Furstenberger G, Senn HJ (2002) Insulin-like growth factors and cancer. Lancet Oncol 3:298–302PubMedGoogle Scholar
  10. 10.
    Rinderknecht E, Humbel RE (1978) The amino acid sequence of human insulin-like growth factor I and its structural homology with proinsulin. J Biol Chem 253:2769–2776PubMedGoogle Scholar
  11. 11.
    Blundell TL, Bedarkar S, Rinderknecht E, Humbel RE (1978) Insulin-like growth factor: a model for tertiary structure accounting for immunoreactivity and receptor binding. Proc Natl Acad Sci USA 75:180–184PubMedGoogle Scholar
  12. 12.
    Yu H, Rohan T (2000) Role of the insulin-like growth factor family in cancer development and progression. J Natl Cancer Inst 92:1472–1489PubMedGoogle Scholar
  13. 13.
    Mohan S, Baylink DJ (2002) IGF-binding proteins are multifunctional and act via IGF-dependent and -independent mechanisms. J Endocrinol 175:19–31PubMedGoogle Scholar
  14. 14.
    LeRoith D, Adamo M, Werner H, Roberts C (1991) Insulinlike growth factors and their receptors as growth regulators in normal physiology and pathogenic states. Trends Endocrinol Metab 2:134–139Google Scholar
  15. 15.
    Olsen SF, Halldorsson TI, Willett WC et al (2007) Milk consumption during pregnancy is associated with increased infant size at birth: prospective cohort study. Am J Clin Nutr 86:1104–1110PubMedGoogle Scholar
  16. 16.
    Han VK, D’Ercole AJ, Lund PK (1987) Cellular localization of somatomedin (insulin-like growth factor) messenger RNA in the human fetus. Science 236:193–197PubMedGoogle Scholar
  17. 17.
    Randhawa R, Cohen P (2005) The role of the insulin-like growth factor system in prenatal growth. Mol Genet Metab 86:84–90PubMedGoogle Scholar
  18. 18.
    Javaid M, Godfrey K, Taylor P et al (2004) Umbilical venous IGF-1 concentration, neonatal bone mass, and body composition. J Bone Miner Res 19:56–63PubMedGoogle Scholar
  19. 19.
    Wollmann HA (2000) Growth hormone and growth factors during perinatal life. Horm Res 53:50–54PubMedGoogle Scholar
  20. 20.
    Baker J, Liu JP, Robertson EJ, Efstratiadis A (1993) Role of insulin-like growth factors in embryonic and postnatal growth. Cell 75:73–82PubMedGoogle Scholar
  21. 21.
    Gluckman PD (1995) Clinical review 68: the endocrine regulation of fetal growth in late gestation: the role of insulin-like growth factors. J Clin Endocrinol Metab 80:1047–1050PubMedGoogle Scholar
  22. 22.
    Bennett A, Wilson DM, Liu F, Nagashima R, Rosenfeld RG, Hintz RL (1983) Levels of insulin-like growth factors I and II in human cord blood. J Clin Endocrinol Metab 57:609–612PubMedGoogle Scholar
  23. 23.
    Fant M, Salafia C, Baxter RC et al (1993) Circulating levels of IGFs and IGF binding proteins in human cord serum: relationships to intrauterine growth. Regul Pept 48:29–39PubMedGoogle Scholar
  24. 24.
    Ong K, Kratzsch J, Kiess W, Costello M, Scott C, Dunger D (2000) Size at birth and cord blood levels of insulin, insulin-like growth factor I (IGF-I), IGF-II, IGF-binding protein-1 (IGFBP-1), IGFBP-3, and the soluble IGF-II/mannose-6-phosphate receptor in term human infants. The ALSPAC study team. Avon longitudinal study of pregnancy and childhood. J Clin Endocrinol Metab 85:4266–4269PubMedGoogle Scholar
  25. 25.
    Shibata A, Harris DT, Billings PR (2002) Concentrations of estrogens and IGFs in umbilical cord blood plasma: a comparison among Caucasian, Hispanic, and Asian-American females. J Clin Endocrinol Metab 87:810–815PubMedGoogle Scholar
  26. 26.
    Gluckman PD, Johnson-Barrett JJ, Butler JH, Edgar BW, Gunn TR (1983) Studies of insulin-like growth factor-I and -II by specific radioligand assays in umbilical cord blood. Clin Endocrinol (Oxf) 19:405–413Google Scholar
  27. 27.
    Osorio M, Torres J, Moya F et al (1996) Insulin-like growth factors (IGFs) and IGF binding proteins-1, -2, and -3 in newborn serum: relationships to fetoplacental growth at term. Early Hum Dev 46:15–26PubMedGoogle Scholar
  28. 28.
    Klauwer D, Blum WF, Hanitsch S, Rascher W, Lee PD, Kiess W (1997) IGF-I, IGF-II, free IGF-I and IGFBP-1, -2 and -3 levels in venous cord blood: relationship to birthweight, length and gestational age in healthy newborns. Acta Paediatr 86:826–833PubMedGoogle Scholar
  29. 29.
    Christou H, Connors JM, Ziotopoulou M et al (2001) Cord blood leptin and insulin-like growth factor levels are independent predictors of fetal growth. J Clin Endocrinol Metab 86:935–938PubMedGoogle Scholar
  30. 30.
    Olausson H, Lof M, Brismar K, Lewitt M, Forsum E, Sohlstrom A (2008) Longitudinal study of the maternal insulin-like growth factor system before, during and after pregnancy in relation to fetal and infant weight. Horm Res 69:99–106PubMedGoogle Scholar
  31. 31.
    Liu JP, Baker J, Perkins AS, Robertson EJ, Efstratiadis A (1993) Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r). Cell 75:59–72PubMedGoogle Scholar
  32. 32.
    DeChiara TM, Robertson EJ, Efstratiadis A (1991) Parental imprinting of the mouse insulin-like growth factor II gene. Cell 64:849–859PubMedGoogle Scholar
  33. 33.
    DeChiara TM, Efstratiadis A, Robertson EJ (1990) A growth-deficiency phenotype in heterozygous mice carrying an insulin-like growth factor II gene disrupted by targeting. Nature 345:78–80PubMedGoogle Scholar
  34. 34.
    Liu Y-J, Tsushima T, Minei S et al (1996) Insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBP-1, -2 and -3) in diabetic pregnancy: relationship to macrosomia. Endocr J 43:221–231Google Scholar
  35. 35.
    Constancia M, Angiolini E, Sandovici I et al (2005) Adaptation of nutrient supply to fetal demand in the mouse involves interaction between the Igf2 gene and placental transporter systems. Proc Natl Acad Sci USA 102:19219–19224PubMedGoogle Scholar
  36. 36.
    Kniss DA, Shubert PJ, Zimmerman PD, Landon MB, Gabbe SG (1994) Insulinlike growth factors. Their regulation of glucose and amino acid transport in placental trophoblasts isolated from first-trimester chorionic villi. J Reprod Med 39:249–256PubMedGoogle Scholar
  37. 37.
    Ravenel JD, Broman KW, Perlman EJ et al (2001) Loss of imprinting of insulin-like growth factor-II (IGF2) gene in distinguishing specific biologic subtypes of Wilms tumor. J Natl Cancer Inst 93:1698–1703PubMedGoogle Scholar
  38. 38.
    Kaneda A, Wang CJ, Cheong R et al (2007) Enhanced sensitivity to IGF-II signaling links loss of imprinting of IGF2 to increased cell proliferation and tumor risk. Proc Natl Acad Sci USA 104:20926–20931PubMedGoogle Scholar
  39. 39.
    Ullrich A, Gray A, Tam AW et al (1986) Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity. EMBO J 5:2503–2512PubMedGoogle Scholar
  40. 40.
    Germain-Lee EL, Janicot M, Lammers R, Ullrich A, Casella SJ (1992) Expression of a type I insulin-like growth factor receptor with low affinity for insulin-like growth factor II. Biochem J 281(Pt 2):413–417PubMedGoogle Scholar
  41. 41.
    Sferruzzi-Perri AN, Owens JA, Standen P, Roberts CT (2008) Maternal insulin-like growth factor-II promotes placental functional development via the type 2 IGF receptor in the guinea pig. Placenta 29:347–355PubMedGoogle Scholar
  42. 42.
    Barlow DP, Stoger R, Herrmann BG, Saito K, Schweifer N (1991) The mouse insulin-like growth factor type-2 receptor is imprinted and closely linked to the Tme locus. Nature 349:84–87PubMedGoogle Scholar
  43. 43.
    Latham KE, Doherty AS, Scott CD, Schultz RM (1994) Igf2r and Igf2 gene expression in androgenetic, gynogenetic, and parthenogenetic preimplantation mouse embryos: absence of regulation by genomic imprinting. Genes Dev 8:290–299PubMedGoogle Scholar
  44. 44.
    Wang ZQ, Fung MR, Barlow DP, Wagner EF (1994) Regulation of embryonic growth and lysosomal targeting by the imprinted Igf2/Mpr gene. Nature 372:464–467PubMedGoogle Scholar
  45. 45.
    Han VK (1996) The ontogeny of growth hormone, insulin-like growth factors and sex steroids: molecular aspects. Horm Res 45:61–66PubMedGoogle Scholar
  46. 46.
    Pannier EM, Irwin JC, Giudice LC (1994) Insulin-like growth factor-binding proteins in the human fetus: tissue-specific protein secretion, immunologic characterization, and gene expression. Am J Obstet Gynecol 171:746–752PubMedGoogle Scholar
  47. 47.
    Chevallier B, Lagarde A, Degrelle H, Belaisch-Allart J, Giraudet P, Gallet JP (1998) Insulin-like growth factor binding protein 1 level in amniotic fluid: correlation with birth weight. Biol Neonate 73:404–406PubMedGoogle Scholar
  48. 48.
    Westwood M (1999) Role of insulin-like growth factor binding protein 1 in human pregnancy. Rev Reprod 4:160–167PubMedGoogle Scholar
  49. 49.
    Westwood M, Gibson JM, Davies AJ, Young RJ, White A (1994) The phosphorylation pattern of insulin-like growth factor-binding protein-1 in normal plasma is different from that in amniotic fluid and changes during pregnancy. J Clin Endocrinol Metab 79:1735–1741PubMedGoogle Scholar
  50. 50.
    Wang HS, Perry LA, Kanisius J, Iles RK, Holly JM, Chard T (1991) Purification and assay of insulin-like growth factor-binding protein-1: measurement of circulating levels throughout pregnancy. J Endocrinol 128:161–168PubMedGoogle Scholar
  51. 51.
    Westwood M, Gibson JM, White A (1997) Purification and characterization of the insulin-like growth factor-binding protein-1 phosphoform found in normal plasma. Endocrinology 138:1130–1136PubMedGoogle Scholar
  52. 52.
    Tisi DK, Liu XJ, Wykes LJ, Skinner CD, Koski KG (2005) Insulin-like growth factor II and binding proteins 1 and 3 from second trimester human amniotic fluid are associated with infant birth weight. J Nutr 135:1667–1672PubMedGoogle Scholar
  53. 53.
    Giudice LC, Martina NA, Crystal RA, Tazuke S, Druzin M (1997) Insulin-like growth factor binding protein-1 at the maternal-fetal interface and insulin-like growth factor-I, insulin-like growth factor-II, and insulin-like growth factor binding protein-1 in the circulation of women with severe preeclampsia. Am J Obstet Gynecol 176:751–757PubMedGoogle Scholar
  54. 54.
    Langford K, Blum W, Nicolaides K, Jones J, McGregor A, Miell J (1994) The pathophysiology of the insulin-like growth factor axis in fetal growth failure: a basis for programming by undernutrition? Eur J Clin Invest 24:851–856PubMedGoogle Scholar
  55. 55.
    Ochoa R, Zarate A, Hernandez M, Galvan R, Basurto L (2001) Serum leptin and somatotropin components correlate with neonatal birth weight. Gynecol Obstet Invest 52:243–247PubMedGoogle Scholar
  56. 56.
    Orbak Z, Darcan S, Coker M, Goksen D (2001) Maternal and fetal serum insulin-like growth factor-I (IGF-I) IGF binding protein-3 (IGFBP-3), leptin levels and early postnatal growth in infants born asymmetrically small for gestational age. J Pediatr Endocrinol Metab 14:1119–1127PubMedGoogle Scholar
  57. 57.
    Guler HP, Zapf J, Schmid C, Froesch ER (1989) Insulin-like growth factors I and II in healthy man. Estimations of half-lives and production rates. Acta Endocrinol 121:753–758PubMedGoogle Scholar
  58. 58.
    Rajah R, Valentinis B, Cohen P (1997) Insulin-like growth factor (IGF)-binding protein-3 induces apoptosis and mediates the effects of transforming growth factor-beta1 on programmed cell death through a p53- and IGF-independent mechanism. J Biol Chem 272:12181–12188PubMedGoogle Scholar
  59. 59.
    Gill ZP, Perks CM, Newcomb PV, Holly JM (1997) Insulin-like growth factor-binding protein (IGFBP-3) predisposes breast cancer cells to programmed cell death in a non-IGF-dependent manner. J Biol Chem 272:25602–25607PubMedGoogle Scholar
  60. 60.
    Butt AJ, Firth SM, Baxter RC (1999) The IGF axis and programmed cell death. Immunol Cell Biol 77:256–262PubMedGoogle Scholar
  61. 61.
    Oh Y, Muller HL, Lamson G, Rosenfeld RG (1993) Insulin-like growth factor (IGF)-independent action of IGF-binding protein-3 in Hs578T human breast cancer cells. Cell surface binding and growth inhibition. J Biol Chem 268:14964–14971PubMedGoogle Scholar
  62. 62.
    Collett-Solberg PF, Cohen P (1996) The role of the insulin-like growth factor binding proteins and the IGFBP proteases in modulating IGF action. Endocrinol Metab Clin North Am 25:591–614PubMedGoogle Scholar
  63. 63.
    Mohnike K, Klube U, Mittler U, Aumann V, Vorwerk P, Blum W (1996) Serum levels of insulin-like growth factor-I, -II and insulin-like growth factor binding proteins -2 and -3 in children with acute lymphoblastic leukaemia. Eur J Pediatr 155:81–86PubMedGoogle Scholar
  64. 64.
    Bang P, Westgren M, Schwander J, Blum WF, Rosenfeld RG, Stangenberg M (1994) Ontogeny of insulin-like growth factor-binding protein-1, -2, and -3: quantitative measurements by radioimmunoassay in human fetal serum. Pediatr Res 36:528–536PubMedGoogle Scholar
  65. 65.
    Vorwerk P, Wex H, Bessert C, Hohmann B, Schmidt U, Mittler U (2003) Loss of imprinting of IGF-II gene in children with acute lymphoblastic leukemia. Leuk Res 27:807–812PubMedGoogle Scholar
  66. 66.
    Elmlinger MW, Sanatani MS, Bell M, Dannecker GE, Ranke MB (1998) Elevated insulin-like growth factor (IGF) binding protein (IGFBP)-2 and IGFBP-4 expression of leukemic T-cells is affected by autocrine/paracrine IGF-II action but not by IGF type I receptor expression. Eur J Endocrinol 138:337–343PubMedGoogle Scholar
  67. 67.
    Wex H, Ahrens D, Hohmann B, Redlich A, Mittler U, Vorwerk P (2005) Insulin-like growth factor-binding protein 4 in children with acute lymphoblastic leukemia. Int J Hematol 82:137–142PubMedGoogle Scholar
  68. 68.
    Kiefer MC, Schmid C, Waldvogel M et al (1992) Characterization of recombinant human insulin-like growth factor binding proteins 4, 5, and 6 produced in yeast. J Biol Chem 267:12692–12699PubMedGoogle Scholar
  69. 69.
    Kelley KM, Oh Y, Gargosky SE et al (1996) Insulin-like growth factor-binding proteins (IGFBPs) and their regulatory dynamics. Int J Biochem Cell Biol 28:619–637PubMedGoogle Scholar
  70. 70.
    Schneider MR, Wolf E, Hoeflich A, Lahm H (2002) IGF-binding protein-5: flexible player in the IGF system and effector on its own. J Endocrinol 172:423–440PubMedGoogle Scholar
  71. 71.
    Bach LA (2005) IGFBP-6 five years on; not so ‘forgotten’? Growth Horm IGF Res 15:185–192PubMedGoogle Scholar
  72. 72.
    Hwa V, Oh Y, Rosenfeld RG (1999) The insulin-like growth factor-binding protein (IGFBP) superfamily. Endocr Rev 20:761–787PubMedGoogle Scholar
  73. 73.
    Laursen LS, Overgaard MT, Soe R et al (2001) Pregnancy-associated plasma protein-A (PAPP-A) cleaves insulin-like growth factor binding protein (IGFBP)-5 independent of IGF: implications for the mechanism of IGFBP-4 proteolysis by PAPP-A. FEBS Lett 504:36–40PubMedGoogle Scholar
  74. 74.
    Sun IY, Overgaard MT, Oxvig C, Giudice LC (2002) Pregnancy-associated plasma protein A proteolytic activity is associated with the human placental trophoblast cell membrane. J Clin Endocrinol Metab 87:5235–5240PubMedGoogle Scholar
  75. 75.
    Giudice LC, Conover CA, Bale L et al (2002) Identification and regulation of the IGFBP-4 protease and its physiological inhibitor in human trophoblasts and endometrial stroma: evidence for paracrine regulation of IGF-II bioavailability in the placental bed during human implantation. J Clin Endocrinol Metab 87:2359–2366PubMedGoogle Scholar
  76. 76.
    Kwik M, Morris J (2003) Association between first trimester maternal serum pregnancy associated plasma protein-A and adverse pregnancy outcome. Aust N Z J Obstet Gynaecol 43:438–442PubMedGoogle Scholar
  77. 77.
    Santolaya-Forgas J, De Leon JA, Cullen Hopkins R, Castracane VD, Kauffman RP, Sifuentes GA (2004) Low pregnancy-associated plasma protein-a at 10(+1) to 14(+6) weeks of gestation and a possible mechanism leading to miscarriage. Fetal Diagn Ther 19:456–461PubMedGoogle Scholar
  78. 78.
    Pedersen JF, Sorensen S, Ruge S (1995) Human placental lactogen and pregnancy-associated plasma protein A in first trimester and subsequent fetal growth. Acta Obstet Gynecol Scand 74:505–508PubMedGoogle Scholar
  79. 79.
    Smith GC, Stenhouse EJ, Crossley JA, Aitken DA, Cameron AD, Connor JM (2002) Early pregnancy levels of pregnancy-associated plasma protein a and the risk of intrauterine growth restriction, premature birth, preeclampsia, and stillbirth. J Clin Endocrinol Metab 87:1762–1767PubMedGoogle Scholar
  80. 80.
    Canini S, Prefumo F, Pastorino D et al (2008) Association between birth weight and first-trimester free beta-human chorionic gonadotropin and pregnancy-associated plasma protein A. Fertil Steril 89:174–178PubMedGoogle Scholar
  81. 81.
    Conover CA, Bale LK, Overgaard MT et al (2004) Metalloproteinase pregnancy-associated plasma protein A is a critical growth regulatory factor during fetal development. Development 131:1187–1194PubMedGoogle Scholar
  82. 82.
    Coppock HA, White A, Aplin JD, Westwood M (2004) Matrix metalloprotease-3 and -9 proteolyze insulin-like growth factor-binding protein-1. Biol Reprod 71:438–443PubMedGoogle Scholar
  83. 83.
    Overgaard MT, Boldt HB, Laursen LS, Sottrup-Jensen L, Conover CA, Oxvig C (2001) Pregnancy-associated plasma protein-A2 (PAPP-A2), a novel insulin-like growth factor-binding protein-5 proteinase. J Biol Chem 276:21849–21853PubMedGoogle Scholar
  84. 84.
    Arguelles B, Barrios V, Pozo J, Munoz MT, Argente J (2000) Modifications of growth velocity and the insulin-like growth factor system in children with acute lymphoblastic leukemia: a longitudinal study. J Clin Endocrinol Metab 85:4087–4092PubMedGoogle Scholar
  85. 85.
    Vorwerk P, Mohnike K, Wex H et al (2005) Insulin-like growth factor binding protein-2 at diagnosis of childhood acute lymphoblastic leukemia and the prediction of relapse risk. J Clin Endocrinol Metab 90:3022–3027PubMedGoogle Scholar
  86. 86.
    Mohnike K, Skjaeraek C, Wex H et al (1998) Low serum in leukemia is due to sequestration. Horm Res 50:94Google Scholar
  87. 87.
    Zumkeller W, Burdach S (1999) The insulin-like growth factor system in normal and malignant hematopoietic cells. Blood 94:3653–3657PubMedGoogle Scholar
  88. 88.
    Zumkeller W (2002) The insulin-like growth factor system in hematopoietic cells. Leuk Lymphoma 43:487–491PubMedGoogle Scholar
  89. 89.
    Barrios V, Buno M, Pozo J, Munoz MT, Argente J (2000) Insulin-like growth factor-binding protein-2 levels in pediatric patients with growth hormone deficiency, eating disorders and acute lymphoblastic leukemia. Horm Res 53:221–227PubMedGoogle Scholar
  90. 90.
    Muller HL, Oh Y, Gargosky SE, Wilson KF, Lehrnbecher T, Rosenfeld RG (1994) Insulin-like growth factor binding protein-3 concentrations and insulin-like growth factor binding protein-3 protease activity in sera of patients with malignant solid tumors or leukemia. Pediatr Res 35:720–724PubMedGoogle Scholar
  91. 91.
    Van Doorn J, Cornelissen AJ, Van Buul-Offers SC (2001) Plasma levels of insulin-like growth factor binding protein-4 (IGFBP-4) under normal and pathological conditions. Clin Endocrinol (Oxf) 54:655–664Google Scholar
  92. 92.
    Hattori H, Matsuzaki A, Suminoe A et al (2000) Genomic imprinting of insulin-like growth factor-2 in infant leukemia and childhood neuroblastoma. Cancer 88:2372–2377PubMedGoogle Scholar
  93. 93.
    Dawczynski K, Steinbach D, Wittig S, Pfaffendorf N, Kauf E, Zintl F (2008) Expression of components of the IGF axis in childhood acute myelogenous leukemia. Pediatr Blood Cancer 50:24–28PubMedGoogle Scholar
  94. 94.
    Schuz J, Kaletsch U, Meinert R, Kaatsch P, Michaelis J (2001) High-birth weight and other risk factors for Wilms tumour: results of a population-based case–control study. Eur J Pediatr 160:333–338PubMedGoogle Scholar
  95. 95.
    Yeazel MW, Ross JA, Buckley JD, Woods WG, Ruccione K, Robison LL (1997) High birth weight and risk of specific childhood cancers: a report from the Children’s Cancer Group. J Pediatr 131:671–677PubMedGoogle Scholar
  96. 96.
    Olshan AF, Breslow NE, Falletta JM et al (1993) Risk factors for Wilms tumor. Report from the National Wilms Tumor Study. Cancer 72:938–944PubMedGoogle Scholar
  97. 97.
    Lee J, Chia K-S, Cheung K-H, Chia S-E, Lee H-P (2004) Birthweight and the risk of early childhood cancer among Chinese in Singapore. Int J Cancer 110:465–467PubMedGoogle Scholar
  98. 98.
    Schuz J, Kaatsch P, Kaletsch U, Meinert R, Michaelis J (1999) Association of childhood cancer with factors related to pregnancy and birth. Int J Epidemiol 28:631–639PubMedGoogle Scholar
  99. 99.
    Schuz J, Forman MR (2007) Birthweight by gestational age and childhood cancer. Cancer Causes Control 18:655–663PubMedGoogle Scholar
  100. 100.
    Yuan E, Li CM, Yamashiro DJ et al (2005) Genomic profiling maps loss of heterozygosity and defines the timing and stage dependence of epigenetic and genetic events in Wilms’ tumors. Mol Cancer Res 3:493–502PubMedGoogle Scholar
  101. 101.
    Leisenring WM, Breslow NE, Evans IE, Beckwith JB, Coppes MJ, Grundy P (1994) Increased birth weights of National Wilms’ Tumor Study patients suggest a growth factor excess. Cancer Res 54:4680–4683PubMedGoogle Scholar
  102. 102.
    Hoyme HE, Seaver LH, Jones KL, Procopio F, Crooks W, Feingold M (1998) Isolated hemihyperplasia (hemihypertrophy): report of a prospective multicenter study of the incidence of neoplasia and review. Am J Med Genet 79:274–278PubMedGoogle Scholar
  103. 103.
    Morison IM, Becroft DM, Taniguchi T, Woods CG, Reeve AE (1996) Somatic overgrowth associated with overexpression of insulin-like growth factor II. Nat Med 2:311–316PubMedGoogle Scholar
  104. 104.
    Rainier S, Johnson LA, Dobry CJ, Ping AJ, Grundy PE, Feinberg AP (1993) Relaxation of imprinted genes in human cancer. Nature 362:747–749PubMedGoogle Scholar
  105. 105.
    Brown KW, Power F, Moore B, Charles AK, Malik KTA (2008) Frequency and timing of loss of imprinting at 11p13 and 11p15 in Wilms’ tumor development. Mol Cancer Res 6:1114–1123PubMedGoogle Scholar
  106. 106.
    Zumkeller W, Schwander J, Mitchell CD, Morrell DJ, Schofield PN, Preece MA (1993) Insulin-like growth factor (IGF)-I, -II and IGF binding protein-2 (IGFBP-2) in the plasma of children with Wilms’ tumour. Eur J Cancer 29A:1973–1977PubMedGoogle Scholar
  107. 107.
    Haselbacher GK, Irminger JC, Zapf J, Ziegler WH, Humbel RE (1987) Insulin-like growth factor II in human adrenal pheochromocytomas and Wilms tumors: expression at the mRNA and protein level. Proc Natl Acad Sci USA 84:1104–1106PubMedGoogle Scholar
  108. 108.
    Daling JR, Starzyk P, Olshan AF, Weiss NS (1984) Birth weight and the incidence of childhood cancer. J Natl Cancer Inst 72:1039–1041PubMedGoogle Scholar
  109. 109.
    Lapunzina P (2005) Risk of tumorigenesis in overgrowth syndromes: a comprehensive review. Am J Med Genet C Semin Med Genet 137:53–71Google Scholar
  110. 110.
    Neglia JP, Smithson WA, Gunderson P, King FL, Singher LJ, Robison LL (1988) Prenatal and perinatal risk factors for neuroblastoma. A case–control study. Cancer 61:2202–2206PubMedGoogle Scholar
  111. 111.
    Johnson CC, Spitz MR (1985) Neuroblastoma: case–control analysis of birth characteristics. J Natl Cancer Inst 74:789–792PubMedGoogle Scholar
  112. 112.
    Wada M, Seeger RC, Mizoguchi H, Koeffler HP (1995) Maintenance of normal imprinting of H19 and IGF2 genes in neuroblastoma. Cancer Res 55:3386–3388PubMedGoogle Scholar
  113. 113.
    Hedborg F, Ohlsson R, Sandstedt B, Grimelius L, Hoehner JC, Pahlman S (1995) IGF2 expression is a marker for paraganglionic/SIF cell differentiation in neuroblastoma. Am J Pathol 146:833–847PubMedGoogle Scholar
  114. 114.
    Sullivan KA, Castle VP, Hanash SM, Feldman EL (1995) Insulin-like growth factor II in the pathogenesis of human neuroblastoma. Am J Pathol 147:1790–1798PubMedGoogle Scholar
  115. 115.
    Henry I, Bonaiti-Pellie C, Chehensse V et al (1991) Uniparental paternal disomy in a genetic cancer-predisposing syndrome. Nature 351:665–667PubMedGoogle Scholar
  116. 116.
    Scrable H, Cavenee W, Ghavimi F, Lovell M, Morgan K, Sapienza C (1989) A model for embryonal rhabdomyosarcoma tumorigenesis that involves genome imprinting. Proc Natl Acad Sci USA 86:7480–7484PubMedGoogle Scholar
  117. 117.
    Savitz DA, Ananth CV (1994) Birth characteristics of childhood cancer cases, controls, and their siblings. Pediatr Hematol Oncol 11:587–599PubMedGoogle Scholar
  118. 118.
    Zhan S, Shapiro DN, Helman LJ (1994) Activation of an imprinted allele of the insulin-like growth factor II gene implicated in rhabdomyosarcoma. J Clin Invest 94:445–448PubMedGoogle Scholar
  119. 119.
    Anderson J, Gordon A, McManus A, Shipley J, Pritchard-Jones K (1999) Disruption of imprinted genes at chromosome region 11p15.5 in paediatric rhabdomyosarcoma. Neoplasia 1:340–348PubMedGoogle Scholar
  120. 120.
    El-Badry OM, Minniti C, Kohn EC, Houghton PJ, Daughaday WH, Helman LJ (1990) Insulin-like growth factor II acts as an autocrine growth and motility factor in human rhabdomyosarcoma tumors. Cell Growth Differ 1:325–331PubMedGoogle Scholar
  121. 121.
    Minniti CP, Kohn EC, Grubb JH et al (1992) The insulin-like growth factor II (IGF-II)/mannose 6-phosphate receptor mediates IGF-II-induced motility in human rhabdomyosarcoma cells. J Biol Chem 267:9000–9004PubMedGoogle Scholar
  122. 122.
    Davies SM (1993) Maintenance of genomic imprinting at the IGF2 locus in hepatoblastoma. Cancer Res 53:4781–4783PubMedGoogle Scholar
  123. 123.
    Reynolds P, Urayama KY, Von Behren J, Feusner J (2004) Birth characteristics and hepatoblastoma risk in young children. Cancer 100:1070–1076PubMedGoogle Scholar
  124. 124.
    Oue T, Kubota A, Okuyama H et al (2003) Hepatoblastoma in children of extremely low birth weight: a report from a single perinatal center. J Pediatr Surg 38:134–137PubMedGoogle Scholar
  125. 125.
    Spector LG, Johnson KJ, Soler JT, Puumala SE (2008) Perinatal risk factors for hepatoblastoma. Br J Cancer 98:1570–1573PubMedGoogle Scholar
  126. 126.
    Rainier S, Dobry CJ, Feinberg AP (1995) Loss of imprinting in hepatoblastoma. Cancer Res 55:1836–1838PubMedGoogle Scholar
  127. 127.
    Li X, Adam G, Cui H, Sandstedt B, Ohlsson R, Ekstrom TJ (1995) Expression, promoter usage and parental imprinting status of insulin-like growth factor II (IGF2) in human hepatoblastoma: uncoupling of IGF2 and H19 imprinting. Oncogene 11:221–229PubMedGoogle Scholar
  128. 128.
    Hartmann W, Waha A, Koch A et al (2000) p57(KIP2) is not mutated in hepatoblastoma but shows increased transcriptional activity in a comparative analysis of the three imprinted genes p57(KIP2), IGF2, and H19. Am J Pathol 157:1393–1403PubMedGoogle Scholar
  129. 129.
    Ross JA, Radloff GA, Davies SM (2000) H19 and IGF-2 allele-specific expression in hepatoblastoma. Br J Cancer 82:753–756PubMedGoogle Scholar
  130. 130.
    Albrecht S, von Schweinitz D, Waha A, Kraus JA, von Deimling A, Pietsch T (1994) Loss of maternal alleles on chromosome arm 11p in hepatoblastoma. Cancer Res 54:5041–5044PubMedGoogle Scholar
  131. 131.
    Montagna M, Menin C, Chieco-Bianchi L, D’Andrea E (1994) Occasional loss of constitutive heterozygosity at 11p15.5 and imprinting relaxation of the IGFII maternal allele in hepatoblastoma. J Cancer Res Clin Oncol 120:732–736PubMedGoogle Scholar
  132. 132.
    Gray SG, Eriksson T, Ekstrom C et al (2000) Altered expression of members of the IGF-axis in hepatoblastomas. Br J Cancer 82:1561–1567PubMedGoogle Scholar
  133. 133.
    Emerson JC, Malone KE, Daling JR, Starzyk P (1991) Childhood brain tumor risk in relation to birth characteristics. J Clin Epidemiol 44:1159–1166PubMedGoogle Scholar
  134. 134.
    Kuijten RR, Bunin GR, Nass CC, Meadows AT (1990) Gestational and familial risk factors for childhood astrocytoma: results of a case–control study. Cancer Res 50:2608–2612PubMedGoogle Scholar
  135. 135.
    Mogren I, Malmer B, Tavelin B, Damber L (2003) Reproductive factors have low impact on the risk of different primary brain tumours in offspring. Neuroepidemiology 22:249–254PubMedGoogle Scholar
  136. 136.
    Von Behren J, Reynolds P (2003) Birth characteristics and brain cancers in young children. Int J Epidemiol 32:248–256Google Scholar
  137. 137.
    Heuch JM, Heuch I, Akslen LA, Kvale G (1998) Risk of primary childhood brain tumors related to birth characteristics: a Norwegian prospective study. Int J Cancer 77:498–503PubMedGoogle Scholar
  138. 138.
    Russo VC, Gluckman PD, Feldman EL, Werther GA (2005) The insulin-like growth factor system and its pleiotropic functions in brain. Endocr Rev 26:916–943PubMedGoogle Scholar
  139. 139.
    Wang JY, Del Valle L, Gordon J et al (2001) Activation of the IGF-IR system contributes to malignant growth of human and mouse medulloblastomas. Oncogene 20:3857–3868PubMedGoogle Scholar
  140. 140.
    Del Valle L, Enam S, Lassak A et al (2002) Insulin-like growth factor I receptor activity in human medulloblastomas. Clin Cancer Res 8:1822–1830PubMedGoogle Scholar
  141. 141.
    Ogino S, Kubo S, Abdul-Karim FW, Cohen ML (2001) Comparative immunohistochemical study of insulin-like growth factor II and insulin-like growth factor receptor type 1 in pediatric brain tumors. Pediatr Dev Pathol 4:23–31PubMedGoogle Scholar
  142. 142.
    van Doorn J, Gilhuis HJ, Koster JG et al (2004) Differential patterns of insulin-like growth factor-I and -II mRNA expression in medulloblastoma. Neuropathol Appl Neurobiol 30:503–512PubMedGoogle Scholar
  143. 143.
    Pomeroy SL, Tamayo P, Gaasenbeek M et al (2002) Prediction of central nervous system embryonal tumour outcome based on gene expression. Nature 415:436–442PubMedGoogle Scholar
  144. 144.
    Korshunov A, Neben K, Wrobel G et al (2003) Gene expression patterns in ependymomas correlate with tumor location, grade, and patient age. Am J Pathol 163:1721–1727PubMedGoogle Scholar
  145. 145.
    de Bont JM, van Doorn J, Reddingius RE et al (2008) Various components of the insulin-like growth factor system in tumor tissue, cerebrospinal fluid and peripheral blood of pediatric medulloblastoma and ependymoma patients. Int J Cancer 123:594–600PubMedGoogle Scholar
  146. 146.
    Coles HS, Burne JF, Raff MC (1993) Large-scale normal cell death in the developing rat kidney and its reduction by epidermal growth factor. Development 118:777–784PubMedGoogle Scholar
  147. 147.
    Khandwala HM, McCutcheon IE, Flyvbjerg A, Friend KE (2000) The effects of insulin-like growth factors on tumorigenesis and neoplastic growth. Endocr Rev 21:215–244PubMedGoogle Scholar
  148. 148.
    Pollak MN, Schernhammer ES, Hankinson SE (2004) Insulin-like growth factors and neoplasia. Nat Rev Cancer 4:505–518PubMedGoogle Scholar
  149. 149.
    Baik I, Devito WJ, Ballen K et al (2005) Association of fetal hormone levels with stem cell potential: evidence for early life roots of human cancer. Cancer Res 65:358–363PubMedGoogle Scholar
  150. 150.
    Mori H, Colman SM, Xiao Z et al (2002) Chromosome translocations and covert leukemic clones are generated during normal fetal development. Proc Natl Acad Sci USA 99:8242–8247PubMedGoogle Scholar
  151. 151.
    Sakatani T, Wei M, Katoh M et al (2001) Epigenetic heterogeneity at imprinted loci in normal populations. Biochem Biophys Res Commun 283:1124–1130PubMedGoogle Scholar
  152. 152.
    Cui H, Cruz-Correa M, Giardiello FM et al (2003) Loss of IGF2 imprinting: a potential marker of colorectal cancer risk. Science 299:1753–1755PubMedGoogle Scholar
  153. 153.
    LeRoith D, Roberts CT Jr (2003) The insulin-like growth factor system and cancer. Cancer Lett 195:127–137PubMedGoogle Scholar
  154. 154.
    Myers MG Jr, Sun XJ, Cheatham B et al (1993) IRS-1 is a common element in insulin and insulin-like growth factor-I signaling to the phosphatidylinositol 3′-kinase. Endocrinology 132:1421–1430PubMedGoogle Scholar
  155. 155.
    Tao Y, Pinzi V, Bourhis J, Deutsch E (2007) Mechanisms of disease: signaling of the insulin-like growth factor 1 receptor pathway–therapeutic perspectives in cancer. Nat Clin Prac Oncol 4:591–602Google Scholar
  156. 156.
    LeRoith D, Werner H, Beitner-Johnson D, Roberts CT Jr (1995) Molecular and cellular aspects of the insulin-like growth factor I receptor. Endocr Rev 16:143–163PubMedGoogle Scholar
  157. 157.
    Knudson AG (2001) Two genetic hits (more or less) to cancer. Nat Rev Cancer 1:157–162PubMedGoogle Scholar
  158. 158.
    Schuz J, Kaletsch U, Meinert R, Kaatsch P, Spix C, Michaelis J (2001) Risk factors for neuroblastoma at different stages of disease. Results from a population-based case–control study in Germany. J Clin Epidemiol 54:702–709PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  1. 1.Telethon Institute for Child Health Research, Centre for Child Health ResearchThe University of Western AustraliaWest PerthAustralia

Personalised recommendations