Horm Metab Res 2003; 35(11/12): 667-674
DOI: 10.1055/s-2004-814159
Original
© Georg Thieme Verlag Stuttgart · New York

Adaptations of the IGF System during Malignancy: Human Skeletal Muscle versus the Systemic Environment

E.  J.  Foulstone1 , P.  B.  Savage1 , A.  L.  Crown1 , J.  M.  P.  Holly1 , C.  E.  H.  Stewart1
  • 1Division of Surgery, University of Bristol, Bristol Royal Infirmary, Bristol, BS2 8HW, England
Further Information

Publication History

Received 1 September 2003

Accepted after Revision 14 October 2003

Publication Date:
07 January 2004 (online)

Abstract

Presented in this study are data derived from a unique cohort of patients both with and without cancer, for whom we not only have serum samples, allowing us to investigate systemic factors impacting on skeletal muscle maintenance, but also primary skeletal muscle cultures giving us a model to mimic the in vivo muscle milieu. Possible local effects of autocrine/paracrine and endocrine IGF system components impacting on myoblast growth and differentiation could therefore be assessed. We report for the first time that the decrease in myoblast stem cell numbers seen with normal aging is lost in cancer patients. We further report that serum IGF-I, IGF-II and IGFBP-3 all show positive correlations with myoblast retrieval in control patients, but that with the exception of IGFBP-3 these correlations are lost in malignancy. Indeed IGF-II switches to a negative correlation with myotube formation in malignancy. Furthermore we provide initial evidence to suggest that there is an apparent altered regulation of local IGFBP-3 production during malignancy which may enable satellite cell proliferation, stem cell infiltration or both. Finally we show the importance of investigations not only monitoring the systemic impact of serum factors on skeletal muscle responses but also critically assessing the role that locally produced muscle IGFBP-3 may have on the systemic environment.

References

  • 1 Calman K C. Cancer and cachexia.  Br J Hosp Med. 1982;  27 28-29, 33 - 34
  • 2 Wilmore D W. Catabolic illness.  N Engl J Med. 1991;  325 695-702
  • 3 DeWys W D, Begg C, Lavin P T, Band P R, Bennett J M, Bertino J R, Cohen M H, Douglass H O, Engstrom P F, Ezdinli E Z, Horton J, Johnson G J, Moertel C G, Oken M M, Perlia C, Rosenbaum C, Silverstein M N, Skeel R T, Sponzo R W, Tormey D C. Prognostic effect of weight loss prior to chemotherapy in cancer patients.  Am J of Med. 1980;  9 491-497
  • 4 Florini J R, Magri K A, Ewton D Z, James P L, Grindstaff K. Rotwein PS. ”Spontaneous“ differentiation of skeletal myoblasts is dependent upon autocrine secretion of insulin-like growth factor-II.  J Biol Chem. 1991;  266 15 917-15 923
  • 5 Stewart C EH, Rotwein P. Growth, differentiation, and survival: multiple physiological functions for insulin-like growth factors.  Physiol Rev. 1996;  76 1005-1026
  • 6 Wolf R F, Pearlstone D B, Newman E, Heslin M J, Gonenne A, Burt M, Brennan M F. Growth hormone and insulin reverse net whole body and skeletal muscle protein catabolism in cancer patients.  Ann Surg. 1992;  216 280-290
  • 7 Lieberman S A, Butterfield G E, Harrison D, Hoffman A R. Anabolic effects of recombinant insulin-like growth factor-I in cachetic patients with the acquired immunodeficiency syndrome.  J Clin Endocrinol Metab. 1994;  78 404-410
  • 8 Lee P DK, Pivarnik J M, Bukar J G, Muurahainen N, Berry P S, Skolnik P R, Nerad J L, Kudsk K A, Jackson L, Ellis K J, Gesundheit N. A randomised, placebo-controlled trial of combined insulin-like growth factor-I and low dose growth hormone for wasting associated with human immunodeficiency virus infection.  J Clin Endocrinol Metab. 1996;  81 2968-2975
  • 9 Douglas R G, Gluckman P D, Breier B H, McCall J L, Parry B, Shaw J HF. Effects of recombinant IGF-I on protein and glucose metabolism in rTNF-infused lambs.  Am J Physiol. 1991;  261 E606-E612
  • 10 Ng E-H, Rock C S, Lazarus D D, Stiano-Coico L, Moldawer L L, Lowry S F. Insulin-like growth factor-I preserves host lean tissue mass in cancer cachexia.  Am J Physiol. 1992;  262 R426-R431
  • 11 Cooper R N, Tajbakhsh S, Mouly V, Cossu G, Buckingham M, Butler-Browne G S. In vivo satellite cell activation via Myf5 and MyoD in regenerating mouse skeletal muscle.  J Cell Sci. 1999;  112 2895-2901
  • 12 Crown A L, He X L, Holly J MP, Lightman S L, Stewart C EH. Characterisation of the IGF system in a primary adult human skeletal muscle cell model, and comparison of the effects of insulin and IGF-I on protein metabolism.  J Endocrinol. 2000;  67 403-415
  • 13 Henry R R, Ciardaldi T P, Abrams-Carter L, Mudaliar S, Park K S, Nikoulina S E. Glycogen synthase activity is reduced in cultured skeletal muscle cells of non-insulin dependent diabetes mellitus subjects.  J Clin Invest. 1996;  98 1231-1236
  • 14 Khaled M A, McCutcheon M J, Reddy S, Pearman P L, Hunter G R, Weinsier R L. Electrical impedance in assessing human body composition: the BIA method.  Am J Clin Nutr. 1988;  47 789-792
  • 15 Blau H M, Webster C. Isolation and characterisation of human muscle cells.  Proc Natl Acad Sci USA. 1981;  78 5623-5627
  • 16 Foulstone E J, Savage P B, Crown A L, Holly J MP, Stewart C EH. Role of insulin-like growth factor binding protein-3 (IGFBP-3) in the differentiation of primary human adult skeletal myoblasts.  J Cell Physiol. 2003;  195 70-79
  • 17 Cheetham T D, Holly J M, Baxter R C, Meadows K, Jones J, Taylor A M, Dunger D B. The effects of recombinant human IGF-I administration on concentrations of acid labile subunit, IGF binding protein-3, IGF-I, IGF-II and proteolysis of IGF binding protein-3 in adolescents with insulin-dependent diabetes mellitus.  J Endocrinol. 1998;  57 81-87
  • 18 Elmlinger M W, Dengler T, Weinstock C, Kuehnel W. Endocrine alterations in the aging male.  Clin Chem Lab Med. 2003;  41 934-941
  • 19 Gelato M C, Frost R A. IGFBP-3. Functional and structural implications in aging and wasting syndromes.  Endocrine. 1997;  7 81-85
  • 20 Renault V, Piron-Hamelin G, Forestier C, DiDonna S, Decary S, Hentati F, Saillant G, Butler-Browne G S, Mouly V. Skeletal muscle regeneration and the mitotic clock.  Exp Gerontol. 2000;  35 711-719
  • 21 Lorite M J, Smith H J, Arnold J A, Morris A, Thompson M G, Tisdale M J. Activation of ATP-ubiquitin-dependent proteolysis in skeletal muscle in vivo and murine myoblasts in vitro by a proteolysis-inducing factor (PIF).  Br J Cancer. 2001;  85 297-302
  • 22 Smith H J, Tisdale M J. Induction of apoptosis by a cachetic-factor in murine myotubes and inhibition by eicosapentaenoic acid.  Apoptosis. 2003;  8 161-169
  • 23 Wang Z, Corey E, Hass G M, Higano C S, True L D, Wallace D Jr, Tisdale M J, Vessella R L. Expression of the human cachexia-associated protein (HCAP) in prostate cancer and in a prostate cancer animal model of cachexia.  Int J Cancer. 2003;  105 123-129
  • 24 Schultz E, Albright D J, Jaryszak D L, David T L. Survival of satellite cells in whole muscle transplants.  Anatomical Record. 1988;  222 12-17
  • 25 Gussoni E, Soneoka Y, Strickland C D, Buzney E A, Khan M K, Flint A F, Kunkel L M, Mulligan R C. Dystrophin expression in the mdx mouse restored by stem cell transplantation.  Nature. 1999;  401 390-394
  • 26 Carlson B M, Dedkov E I, Borisov A B, Faulkner J A. Skeletal muscle regeneration in very old rats.  J Gerontol A Biol Sci Med Sci. 2001;  56 B224-233
  • 27 Johnson B J, White M E, Hathaway M R, Dayton W R. Decreased steady-state insulin-like binding protein-3 (IGFBP-3) mRNA level is associated with differentiation of cultured porcine myogenic cells.  J Cell Physiol. 1999;  179 237-243
  • 28 Gill Z P, Perks C M, Newcomb P V, Holly J M. 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. 1997;  272 25 602-25 607
  • 29 Perks C M, McCraig C, Holly J M. Differential insulin-like growth factor (IGF)-independent interactions of IGF binding protein-3 and IGF binding protein-5 on apoptosis in human breast cancer cells. Involvement of the mitochondria.  J Cell Biochem. 2001;  80 248-258
  • 30 Spagnoli A, Hwa V, Horton W A, Lunstrum G P, Roberts C T Jr, Chiarelli F, Torello M, Rosenfeld R G. Antiproliferative effects of insulin-like growth factor-binding protein-3 in mesenchymal chondrogenic cell line RCJ3.1C5.18. Relationship to differentiation stage.  J Biol Chem. 2001;  276 5533-5540

Dr. E. Foulstone

Department of Pathology and Microbiology

University of Bristol, School of Medical Sciences · University Walk · Bristol, BS8 1TD · England

Phone: +44(117)3317247

Fax: +44(117)9287896 ·

Email: foulstone@bristol.ac.uk