title: Insulin-like growth factor II acts as an autocrine growth and motility factor in human rhabdomyosarcoma tumors.
abstract: Rhabdomyosarcoma is the most common soft tissue sarcoma of childhood and appears to arise from developing striated muscle-forming cells. Since insulin-like growth factor II (IGF-II) is involved in normal muscle growth and maturation and elevated IGF-II mRNA levels have previously been reported in rhabdomyosarcomas, we have been studying the possible role of IGF-II in the unregulated growth and invasive potential of these embryonal tumors. In this study, we demonstrate that 13 of 14 rhabdomyosarcoma tumors express high levels of IGF-II mRNA relative to normal adult muscle and also express mRNA for the type I IGF receptors on their cell surface, the receptor thought to mediate the effects of IGF-II on muscle cells. We have established several rhabdomyosarcoma cell lines in mitogen-free media and demonstrate that these cells express type I IGF receptors on their cell surface and secrete IGF-II into the media. Exogenous IGF-II is able to stimulate cellular motility in these cell lines as assayed in a modified Boyden chamber. Finally, alpha IR-3, a type I receptor antagonist, inhibits the growth of these cell lines in serum-free media but does not inhibit IGF-II-induced motility of these cells. These data suggest that endogenously produced IGF-II functions as an autocrine growth and motility factor in many rhabdomyosarcoma tumors. The mitogenic actions of IGF-II are mediated through a domain of the type I IGF receptor that is blocked by alpha IR-3. IGF-II-induced motility may be mediated through an alternative signaling pathway.
authors.affiliation: Pediatric Branch, National Cancer Institute, Bethesda, Maryland 20892.
authors.forename: O M
authors.initials: OM
authors.lastname: El-Badry
authors.forename: C
authors.initials: C
authors.lastname: Minniti
authors.forename: E C
authors.initials: EC
authors.lastname: Kohn
authors.forename: P J
authors.initials: PJ
authors.lastname: Houghton
authors.forename: W H
authors.initials: WH
authors.lastname: Daughaday
authors.forename: L J
authors.initials: LJ
authors.lastname: Helman
mesh_terms: D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology / Q000502:physiology*; D009132:Muscles / Q000737:chemistry; D009363:Neoplasm Proteins / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism; D017451:Receptors, Somatomedin; D012208:Rhabdomyosarcoma / Q000737:chemistry / Q000473:pathology*; D012983:Soft Tissue Neoplasms / Q000737:chemistry / Q000473:pathology*
chemical_list: D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D007335:Insulin-Like Growth Factor II