Insulin-like Growth Factor: Current Concepts and New Developments in Cancer Therapy

King, Erin R.; Wong, Kwong-Kwok

doi:10.2174/157489212798357930

Cited by 71 publications

(58 citation statements)

References 161 publications

(147 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The insulin-like growth factor (IGF) family is a complex molecular signaling pathway, which plays an important role in oncogenesis, tumor progression, metastasis and chemoresistance (1). One of the key factors in this family is IGF-1, which is an endocrine and autocrine/paracrine peptide expressed in the majority of cell types and circulating at high levels (2).…”

Section: Introductionmentioning

confidence: 99%

Association of circulating insulin-like growth factor 1 and insulin-like growth factor binding protein 3 with the risk of ovarian cancer: A systematic review and meta-analysis

Wang

Bian

Peng

et al. 2015

Molecular and Clinical Oncology

View full text Add to dashboard Cite

Abstract. Insulin-like growth factor 1 (IGF-1) and its main binding protein (IGFBP-3) in blood have been associated with the risk of several types of cancer. However, epidemiological studies have inconsistent results regarding the association of circulating IGF-1/IGFBP-3 levels with ovarian cancer risk. A systematic review of the prospective studies was conducted using meta-analysis to evaluate the existing evidence. Pubmed and Embase databases were searched to identify the relevant studies published before May 1, 2014. Four highly qualified studies with a total of 627 cases and 1,358 controls were finally included in the meta-analysis. Random effects meta-analysis was conducted by combining study-specific odds ratios (ORs) of ovarian cancer for the highest verses lowest exposure levels. A dose-response association was further assessed by relating the log of ORs for different exposure levels. As a result, the pooled ORs for the highest verses lowest categories of IGF-1/IGFBP-3 were 0.85 [95% confidence interval (CI), 0.51-1.40]/0.78 (95% CI, 0.43-1.40). In the subgroup analyses, the pooled ORs of IGF-1/IGFBP-3 were 1.89 (95% CI, 0.64-5.59)/1.08 (95% CI, 0.50-2.32) for the subgroup with cases diagnosed at <55 years, and 0.74 (95% CI, 0.50-1.08)/0.98 (95% CI, 0.73-1.33) for the subgroup with cases diagnosed at ≥55 years. No linear association between circulating IGF-1/IGFBP-3 levels and ovarian cancer risk was identified. As no significant association of IGF-1/IGFBP-3 with ovarian cancer risk was identified in the present meta-analysis of existing studies, more studies with greater quality are required in the future.

show abstract

Section: Introductionmentioning

confidence: 99%

Association of circulating insulin-like growth factor 1 and insulin-like growth factor binding protein 3 with the risk of ovarian cancer: A systematic review and meta-analysis

Wang

Bian

Peng

et al. 2015

Molecular and Clinical Oncology

View full text Add to dashboard Cite

show abstract

“…The reason for the noticeable increase in pAKT levels in vehicle-treated normoxia mice is not clear, and will require further investigation, although possible activation of AKT due to receptor cross-talk initiated by small-molecule inhibitors, through IGF-1R/epidermal growth factor receptor 1/epidermal growth factor 2/plateletderived growth factor receptor has been described in cancer cell chemoresistance (reviewed in Ref. 42). Our study shows that OSI-906 administration protects against RVH and pulmonary vessel remodeling induced by chronic hypoxia in neonatal mice, and thus, inhibition of the IGF-1/IGF-1R signaling axis may be an approach in the treatment of hypoxia-induced PH in the developing lung.…”

Section: Discussionmentioning

confidence: 99%

Smooth Muscle Insulin-Like Growth Factor-1 Mediates Hypoxia-Induced Pulmonary Hypertension in Neonatal Mice

Sun¹,

Ramchandran²,

Chen

et al. 2016

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

Insulin-like growth factor (IGF)-1 is a potent mitogen of vascular smooth muscle cells (SMCs), but its role in pulmonary vascular remodeling associated with pulmonary hypertension (PH) is not clear. In an earlier study, we implicated IGF-1 in the pathogenesis of hypoxia-induced PH in neonatal mice. In this study, we hypothesized that hypoxia-induced up-regulation of IGF-1 in vascular smooth muscle is directly responsible for pulmonary vascular remodeling and PH. We studied neonatal and adult mice with smooth muscle-specific deletion of IGF-1 and also used an inhibitor of IGF-1 receptor (IGF-1R), OSI-906, in neonatal mice. We found that, in neonatal mice, SMC-specific deletion of IGF-1 or IGF-1R inhibition with OSI-906 attenuated hypoxia-induced pulmonary vascular remodeling in small arteries, right ventricular hypertrophy, and right ventricular systolic pressure. Pulmonary arterial SMCs from IGF-1-deleted mice or after OSI-906 treatment exhibited reduced proliferative potential. However, in adult mice, smooth muscle-specific deletion of IGF-1 had no effect on hypoxia-induced PH. Our data suggest that vascular smooth muscle-derived IGF-1 plays a critical role in hypoxia-induced PH in neonatal mice but not in adult mice. We speculate that the IGF-1/IGF-1R axis is important in pathogenesis of PH in the developing lung and may be amenable to therapeutic manipulation in this age group.Keywords: insulin-like growth factor; pulmonary hypertension; vascular smooth muscle; neonatal; hypoxia Clinical RelevanceWhat this study adds to the field: Using conditional gene deletion in mice, this study shows that loss of insulin-like growth factor (IGF)-1 in smooth muscle cells protects against hypoxia-induced pulmonary vascular remodeling, right ventricular hypertrophy (RVH), and pulmonary hypertension (PH) in neonatal mice. Inhibition of IGF-1 receptor (IGF-1R) with OSI-906 diminished hypoxia-induced RVH and pulmonary vascular remodeling in neonatal mice, indicating that targeting the IGF-1/IGF-1R axis may have therapeutic benefits in the treatment of hypoxic PH in that age group. Pulmonary hypertension (PH) is characterized by a progressive increase in pulmonary arterial pressure accompanied by pulmonary vascular remodeling, leading to right ventricular hypertrophy (RVH) and failure. Proliferation and migration of smooth muscle cells (SMCs) is a characteristic feature of pulmonary vascular remodeling in PH, and dysregulation of many growth factors have been implicated in this process (1, 2). Several growth factors have been implicated in the vascular remodeling and pathogenesis of pulmonary arterial hypertension, and their definitive functions are still being unraveled (reviewed in Refs. 1, 3, 4). Insulin-like growth factor (IGF)-1 is a member of the insulin/IGF family and plays a crucial role in the growth, differentiation, and postnatal development of many tissues and in the regulation of overall growth and metabolism of an organism. IGF-1 is a single-chain polypeptide with a high sequence homology to proinsulin and ...

show abstract

“…This steroid is subsequently converted to LNCaP cells [19,20,41] and considered to be the primary pathway of 444 cholesterol delivery to steroidogenic cells [42,43]. After outlier insulin-induced effects [52,53]. While there was a trend for higher 496 and lower serum GH levels in the Western diet group in intact and 497 castrated mice respectively, there was no significant effect of 498 treatment (P = 0.069; Fig.…”

Section: Introductionmentioning

confidence: 94%

A low carbohydrate, high protein diet suppresses intratumoral androgen synthesis and slows castration-resistant prostate tumor growth in mice

Fokidis¹,

Chin

et al. 2015

The Journal of Steroid Biochemistry and Molecular Biology

View full text Add to dashboard Cite

Insulin-like Growth Factor: Current Concepts and New Developments in Cancer Therapy

Cited by 71 publications

References 161 publications

Association of circulating insulin-like growth factor 1 and insulin-like growth factor binding protein 3 with the risk of ovarian cancer: A systematic review and meta-analysis

Association of circulating insulin-like growth factor 1 and insulin-like growth factor binding protein 3 with the risk of ovarian cancer: A systematic review and meta-analysis

Smooth Muscle Insulin-Like Growth Factor-1 Mediates Hypoxia-Induced Pulmonary Hypertension in Neonatal Mice

A low carbohydrate, high protein diet suppresses intratumoral androgen synthesis and slows castration-resistant prostate tumor growth in mice

Contact Info

Product

Resources

About