Insulin-like growth factor II-mediated proliferation of human neuroblastoma.

Abstract

Neuroblastoma is an embryonal tumor that typically arises in cells of the developing adrenal medulla. IGF-II mRNA is expressed at high levels in the adrenal cortex before birth but it is not detectable until after birth in the adrenal medulla. Neuroblastoma cell lines corresponding to early adrenal medullary precursors did not express IGF-II, although all three cell lines we tested were growth stimulated by IGF-II. Cell lines corresponding to more mature adrenal medullary cells expressed IGF-II, and one, SK-N-AS, grows by an IGF-II autocrine mechanism (J. Clin. Invest. 84:829-839) El-Badry, Romanus, Helman, Cooper, Rechler, and Israel. 1989. An examination of human neuroblastoma tumor tissues for IGF-II gene expression using in situ hybridization histochemistry revealed that IGF-II is expressed by tumor cells in only 5 of 21 neuroblastomas, but is detectable in cells of nonmalignant tissues including adrenal cortical cells, stromal fibroblasts, and eosinophils in all 21 tumors. These findings indicate that IGF-II may function as an autocrine growth factor for some neuroblastomas and as a paracrine growth factor for others. They suggest that the growth regulatory pathways utilized by neuroblastoma mimic those used in the precursor cell type from which individual tumors arise. (J. Clin. Invest. 1991. 87:648-657.)

A Fully Human Insulin-Like Growth Factor-I Receptor Antibody SCH 717454 (Robatumumab) Has Antitumor Activity as a Single Agent and in Combination with Cytotoxics in Pediatric Tumor Xenografts

“…Many pediatric tumors including neuroblastoma, Wilms' tumor, osteosarcoma, and rhabdomyosarcoma are embryonal tumors of the childhood and exhibit increased expression of IGF-II and IGF-IR establishing autocrine loops to perpetuate growth and survival (10)(11)(12)(13)(14)(15). The role of IGF-I in the development of Ewing's sarcoma has also been well documented in addition to the induction of IGF-IR expression by the Ewing's sarcoma fusion protein (16)(17)(18)(19).…”

Silencing of endogenous IGFBP-5 by micro RNA interference affects proliferation, apoptosis and differentiation of neuroblastoma cells

“…22,23 Neuroblastoma (NB), a childhood tumor originating from the embryonic neural crest, is IGF2-sensitive. 24 Although many clinical and genetic markers of NB are commonly used to help the clinicians in defining diagnosis and prognosis of this neoplasia (see for an extensive review Brodeur 25 ), the outcome of stage 3 and 4 patients remains poor. NB preferentially metastasizes at distant sites where a paracrine support of IGF2 is available.…”

“…NB preferentially metastasizes at distant sites where a paracrine support of IGF2 is available. 24 In some aggressive NB tumors as well as in many NB cell lines, autocrine production of IGF2 is detectable. 26 Recently, we demonstrated that IGFBP-5 transcription is stimulated by c-Myb and B-Myb oncoproteins in NB cells through direct and indirect mechanisms.…”

The IGF system in neuroblastoma xenografts: focus on IGF-binding protein-6

“…The insulin-like growth factors, IGF-I and IGF-II, are intricately involved in the proliferation and differentiation of a large number of cell types, and particularly neuroblastoma cells (El-Badry et al 1991, Stewart & Rotwein 1996. Their mitogenic effects are transmitted via a type 1 membrane receptor that has tyrosine kinase activity (De Meyts et al 1994, LeRoith et al 1995.…”