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.

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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

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