Tumour Biology Laboratory

Head of Laboratory

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Overview of research program

Our group was the first to purify and characterise the rat M6P-IGF-II receptor and develop antisera to both rat and human protein, which are regularly distributed widely to national and international researchers. The reagents were used to demonstrate developmental regulation of membrane and soluble M6P/IGF-II receptor in the rat and in regenerating liver. We also developed the only quantitative assay to date for human serum M6P/IGF-II receptor and demonstrated its regulation in development, pregnancy and diabetes. This assay has also been used in international collaborations in growth retardation in children. Our studies also showed that the soluble M6P/IGF-II receptor inhibits cell proliferation,and we are currently investigating the role of soluble receptor as a mediator of anti-proliferative effects.

We have used molecular biology approaches to demonstrate that altering levels of the cellular M6P/IGF-II receptor in cancer cells alters proliferation, motility and invasive potential and profoundly affects tumour growth in nude mice. Current studies are aimed at investigating the genes and pathways involved in the ability of M6P/IGF-II receptor to suppress tumour growth and invasion.

Major funding source

  • National Health and Medical Research Council

Selected publications

Amritraj A, Hawkes C, Phinney AL, Mount HT, Scott CD, Westaway D, Kar S (2009) Altered levels and distribution of IGF-II/M6P receptor and lysosomal enzymes in mutant APP and APP+PS1 transgenic mouse brains. Neurobiology of Aging 30: 54-70

Petry CJ, Ong KK, Wingate DL, Brown J, Scott CD, ALSPAC study team, Jones EY, Pembrey ME, Dunger, DB (2005) Genetic Variation in the type 2 insulin-like growth factor receptor gene and disparity in childhood height. Growth Hormone and IGF Research 15: 363-368

Baron-Hay SE, Boyle F, Ferrier A, Scott CD (2004) Elevated serum IGF binding protein-2 as a prognostic marker in patients with ovarian cancer. Clinical Cancer Research 10:1796-1806

Firth SM and Scott CD (2004) The Role of the M6P/IGF-II Receptor in Cancer: Tumor Suppression or Garbage Disposal? Hormone and Metabolic Research 36: 261-271

Gicquel C, Weiss J, Gaston V, LeBouc Y and Scott CD (2004) Epigenetic abnormalities of the mannose 6-phosphate/IGF2 receptor gene are uncommon in human overgrowth syndromes. Journal of Medical Genetics 41: e4

Lee JS, Weiss J, Martin JL, and Scott CD (2003) Increased expression of the mannose 6-P/IGF-II receptor in breast cancer cells alters tumorigenic properties in vitro and in vivo. Int J Cancer 107: 564-570

O’Gorman DB, Weiss J, Hettiaratchi A, Firth SM and Scott CD (2002) Insulin-like growth factor-II/mannose 6-phosphate receptor overexpression reduces growth of choriocarcinoma cells in vitro and in vivo. Endocrinology 143:4287-4294

Cortisol in Children with Cianfarani S, Geremia C, Scott CD, Germani D (2002) Growth, Insulin-like Growth Factor (IGF) System and Intrauterine Growth Retardation (IUGR). Is Reprogramming of the Hypothalamic-Pituitary-Adrenal Axis (HPAA) Involved in Postnatal Growth? Pediatric Research 51: 94-99

Forbes B, Mcneil KA, Scott CD, Cosgrove L, Wallace JC (2001) Human Insulin-like growth factor-II (IGF-II) A domain residues Ala54 and Leu55 contribute to Type 2 IGF receptor binding specificity. Growth Factors 19 :163-173

Delhanty PJD, Scott CD, Babu S and Baxter RC (2001) Regulation of the acid-labile subunit of the IGF binding protein complex during liver regeneration. Am J Physiol 280:E287-E295

Ong K, Kratzsc J, Kiess W, the ALSPAC team, Costello MC, Scott CD, Dungar D (2000) Size at birth and cord blood levels of insulin, IGF-I, IGF-II, IGFBP-3 and the soluble IGF-II/mannose 6-phosphate receptor in human term infants. J Clin Endocrinol Metab 85: 4266-4269

Scott CD and Weiss J (2000) Inhibition of DNA synthesis by soluble IGF-II/M6P receptor in IGF-II sensitive cell lines. J Cell Physiology 182:62-68

O'Gorman DB, Costello MC, Weiss J, Firth SM, Scott CD (1999) Decreased insulin-like growth factor-II/mannose 6-phosphate receptor expression enhances tumorigenicity in JEG-3 cells. Cancer Research 59: 5692-5694