Expression of insulin-like growth factor receptor, IGF-1, and IGF-2 in primary and metastatic osteosarcoma

Burrow, Sarah; Andrulis, Irene L.; Pollak, Michael; Bell, Robert S.

doi:10.1002/(sici)1096-9098(199809)69:1<21::aid-jso5>3.0.co;2-m

Cited by 95 publications

(70 citation statements)

References 32 publications

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“…IGF-1R and its ligands are overexpressed in human osteosarcoma cell lines [8]. IGF-1R overexpression mediates proliferation, provides apoptosis protection, and has been associated with increased invasiveness and metastasis [56].…”

Section: Discussionmentioning

confidence: 99%

“…Because many of the receptors and downstream signaling molecules are tyrosine kinases [18,22], inhibitors of these kinases are a majority of the most promising anticancer drugs [4,10,21,27]. Although osteosarcoma has not been as well studied as other types of cancer, overexpression in osteosarcoma has been reported for both growth factors and their tyrosine kinase receptors, and overexpression of some of these molecules correlates with metastasis and poor survival in patients with osteosarcoma [5,8,9,15,17,20,23,28,33,36,47,49,60,65].…”

Section: Introductionmentioning

confidence: 99%

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Specific Tyrosine Kinase Inhibitors Regulate Human Osteosarcoma Cells In vitro

Messerschmitt

Rettew

Brookover

et al. 2008

Clin Orthop Relat Res

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Inhibitors of specific tyrosine kinases are attractive lead compounds for development of targeted chemotherapies for many tumors, including osteosarcoma. We asked whether inhibition of specific tyrosine kinases would decrease the motility, colony formation, and/or invasiveness by human osteosarcoma cell lines (TE85, MNNG, 143B, SAOS-2, LM-7). An EGF-R inhibitor reduced motility of all five cell lines by 50% to 80%. In contrast, an IGF-1R inhibitor preferentially reduced motility by 42% in LM-7 cells and a met inhibitor preferentially reduced motility by 80% in MNNG cells. The inhibitors of EGF-R, IGF-1R, and met reduced colony formation by more than 80% in all tested cell lines (TE85, MNNG, 143B). The EGF-R inhibitor reduced invasiveness by 62% in 143B cells. The JAK inhibitor increased motility of SAOS-2 and LM7 cells without affecting colony formation or invasiveness. Inhibitors of HER-2, NGF-R, and PDGF-Rs did not affect motility, invasiveness, or colony formation. These results support the hypothesis that specific tyrosine kinases regulate tumorigenesis and/or metastasis in osteosarcoma.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Specific Tyrosine Kinase Inhibitors Regulate Human Osteosarcoma Cells In vitro

Messerschmitt

Rettew

Brookover

et al. 2008

Clin Orthop Relat Res

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“…For example, in osteosarcomas, several of which (6/8) expressed hCRD-BP, upregulated c-myc expression is frequently not associated with gene amplification. 17 The role of IGF is complex since these tumors show either an abnormal IGF pattern of expression 18 or an altered dependence or sensitivity to these factors. 19,20 In Ewing's sarcomas, c-myc expression is upregulated, conceivably because EWS/ FLI can act as a transactivator of the c-myc promoter.…”

Section: C-myc Mrna Levels In Crd-bp/imp-1-negative and -Positive Tummentioning

confidence: 99%

C‐MYC and IGF‐II mRNA‐binding protein (CRD‐BP/IMP‐1) in benign and malignant mesenchymal tumors

et al. 2001

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Mouse coding region determinant-binding (mCRD-BP)and human IGF-II mRNA-binding 1 (hIMP-1) proteins are orthologous mRNA-binding proteins that recognize c-myc and IGF-II mRNA, respectively, and regulate their expression posttranscriptionally. Here, we confirm that human CRD-BP/IMP-1 binds to c-myc mRNA and that it is predominantly expressed in fetal tissues. Moreover, hCRD-BP/IMP-1 expression was detected in cell lines of neoplastic origin and in selected primary tumors. In a series of 33 malignant and 10 benign mesenchymal tumors, 73% and 40%, respectively, were found to express hCRD-BP/IMP-1. In particular, expression was significant in 14 Ewing's sarcomas, all of which were positive. The data suggest that hCRD-BP/IMP-1 plays a role in abnormal cell proliferation in mesenchymal tumors.

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“…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).…”

Section: Introductionmentioning

confidence: 99%

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

Wang¹,

Lipari²,

Wang³

et al. 2010

Molecular Cancer Therapeutics

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The insulin-like growth factor-I receptor (IGF-IR) and its ligands (IGF-I and IGF-II) have been implicated in the growth, survival, and metastasis of a broad range of malignancies including pediatric tumors. Blocking the IGF-IR action is a potential cancer treatment. A fully human neutralizing monoclonal antibody, SCH 717454 (19D12, robatumumab), specific to IGF-IR, has shown potent antitumor effects in ovarian cancer in vitro and in vivo. In this study, SCH 717454 was evaluated in several pediatric solid tumors including neuroblastoma, osteosarcoma, and rhabdomyosarcoma. SCH 717454 is shown here to downregulate IGF-IR as well as inhibit IGF-IR and insulin receptor substrate-1 phosphorylation in pediatric tumor cells. IGF-IR and insulin receptor substrate-1 phosphorylation in the tumor cells. In vivo, SCH 717454 exhibits activity as a single agent and significantly inhibited growth of neuroblastoma, osteosarcoma, and rhabdomyosarcoma tumor xenografts. Combination of SCH 717454 with cisplatin or cyclophosphamide enhanced both the degree and the duration of the in vivo antitumor activity compared with single-agent treatments. Furthermore, SCH 717454 treatment markedly reduced Ki-67 expression and blood vessel formation in tumor xenografts, showing that the in vivo activity is derived from its inhibition of tumor cell proliferation and angiogenesis activity. Mol Cancer Ther; 9(2); 410-8. ©2010 AACR.

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Expression of insulin-like growth factor receptor, IGF-1, and IGF-2 in primary and metastatic osteosarcoma

Cited by 95 publications

References 32 publications

Specific Tyrosine Kinase Inhibitors Regulate Human Osteosarcoma Cells In vitro

Specific Tyrosine Kinase Inhibitors Regulate Human Osteosarcoma Cells In vitro

C‐MYC and IGF‐II mRNA‐binding protein (CRD‐BP/IMP‐1) in benign and malignant mesenchymal tumors

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

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