Insulin-Like Growth Factor (IGF) Binding Protein-3 Attenuates Prostate Tumor Growth by IGF-Dependent and IGF-Independent Mechanisms

Silha, Josef V.; Sheppard, Patricia; Mishra, Suresh; Gui, Yaoting; Schwartz, Jacquie; Dodd, Janice G.; Murphy, Liam

doi:10.1210/en.2005-1270

Cited by 78 publications

(64 citation statements)

References 36 publications

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“…Recently, Silha et al (2006) reported a reduction in tumor growth in an IGF-independent IGFBP-3 transgenic model. In our study, we detected no IGF-1 in all sublines by enzyme-linked immunosorbent (ELISA) study.…”

Section: Igfbp-3 As An Invasion-metastasis Suppressor P-l Torng Et Almentioning

confidence: 99%

Insulin-like growth factor binding protein-3 (IGFBP-3) acts as an invasion-metastasis suppressor in ovarian endometrioid carcinoma

et al. 2007

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Metastasis and invasion occur in the majority of epithelial ovarian carcinoma at diagnosis. To delineate the molecular signature in ovarian cancer invasion, we established and characterized a human ovarian endometrioid carcinoma (EC) cell line OVTW59-P0 and its invasion-related sublines (P1-P4, in the order of increasing invasive activity). P4 showed faster migration and larger xenograft formation with metastasis than P0. By microarray analysis of different gene expression among P0-P4 sublines, one group of gene was found negatively correlated with cancer invasion. Among these genes, IGFBP-3 was identified as one of the most remarkably suppressed gene that showed lower gene expression in P4 than P0. Re-expression of IGFBP-3 in P4 effectively inhibited cell migration, invasion and metastasis, but did not affect cell proliferation. In 35 patients with EC tumors, low IGFBP-3 expression correlated clinically with higher tumor grade, advanced stage and poor survival. Our results provide evidence and indicate that IGFBP-3 plays an important role as an invasion-metastasis suppressor in ovarian EC.

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Section: Igfbp-3 As An Invasion-metastasis Suppressor P-l Torng Et Almentioning

confidence: 99%

Insulin-like growth factor binding protein-3 (IGFBP-3) acts as an invasion-metastasis suppressor in ovarian endometrioid carcinoma

et al. 2007

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“…IGFBP-3 is the most abundant IGFBP in the blood and was also described as having 'IGF-independent' functions since IGFBP-3 was shown to exhibit proapoptotic (Rajah et al 1997, Butt et al 2000, Williams et al 2007) and anti-proliferative functions (Oh et al 1995, Boyle et al 2001, Silha et al 2006, Alami et al 2008, and was described to be a suppressor of angiogenesis (Liu et al 2007). Various studies indicated that IGFBP-3 also acts as an anti-cancer molecule in prostate cancer (Rajah et al 1997, Bhattacharyya et al 2006, Kojima et al 2006, Liu et al 2007, Silha et al 2006, Peng et al 2007. Furthermore, serum IGFBP-3 may also modulate prostate carcinogenesis, although case-control studies correlating IGFBP-3 concentrations in the blood circulation and prostate cancer risk are contradictory (Renehan et al 2004).…”

Section: Introductionmentioning

confidence: 99%

Novel mechanism of IGF-binding protein-3 action on prostate cancer cells: inhibition of proliferation, adhesion, and motility

Massoner¹,

Colleselli²,

Matscheski³

et al. 2009

Endocrine-Related Cancer

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IGF-binding protein-3 (IGFBP-3) is a modulator of the IGF-signaling pathway and was described as an anti-cancer agent in prostate cancer. The molecular mechanisms underlying these effects remained, however, largely undefined. We analyzed the influence of recombinant IGFBP-3 on cell proliferation of PC3, Du145, and LNCaP prostate cancer cells. As expected, IGFBP-3 inhibited IGF-stimulated cell proliferation by blocking IGF-mediated proliferation signals, but we observed an IGF-independent inhibitory effect of IGFBP-3 on prostate cancer cell proliferation in long-term cultures. We further investigated the influence of IGFBP-3 on adhesion, motility, and invasion of prostate cancer cells using adhesion assays, live-cell imaging techniques, and matrigel invasion measurements. There was a clear inhibitory effect of IGFBP-3 on tumor cell adhesion to extracellular matrix components in the presence and absence of IGF, whereas cell-cell adhesion was not affected. The same inhibitory effect of IGFBP-3 was determined on cell motility when realtime cell movements were followed. In addition, IGFBP-3 was able to inhibit tumor cell invasion through matrigel. In summary, we show that IGFBP-3 inhibits proliferation, adhesion, migration, and invasion processes of prostate tumor cells. These newly described mechanisms of IGFBP-3 can be of importance for tumor progression and support a role of IGFBP-3 in therapeutic settings.

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“…In vivo models suggest that the inhibitory effects of IGFBP-3 on cancer were 398 both IGF-dependent and IGF-independent. IGFBP-3 deletion increased the number of metastases in 399 a prostate cancer mouse model (Mehta, et al 2011), whereas overexpression of both wild-type and 400 a mutant IGFBP-3 that does not bind IGFs attenuated prostate cancer growth (Silha, et al 2006). 401…”

mentioning

confidence: 99%

40 YEARS OF IGF1: IGF-binding proteins

Bach

2018

Journal of Molecular Endocrinology

192

111

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Insulin-like growth factor binding proteins (IGFBPs) 1-6 bind IGFs but not insulin with high affinity. They were initially identified as serum carriers and passive inhibitors of IGF actions.However, subsequent studies showed that, although IGFBPs inhibit IGF actions in many circumstances, they may also potentiate these actions. IGFBPs are widely expressed in most tissues, and they are flexible endocrine and autocrine/paracrine regulators of IGF activity, which is essential for this important physiological system. More recently, individual IGFBPs have been shown to have IGF-independent actions. Mechanisms underlying these actions include (i) interaction with non-IGF proteins in compartments including the extracellular space and matrix, the cell surface and intracellularly; (ii) interaction with and modulation of other growth factor pathways including EGF, TGF-β and VEGF; and (iii) direct or indirect transcriptional effects following nuclear entry of IGFBPs. Through these IGF-dependent and IGF-independent actions, IGFBPs modulate essential cellular processes including proliferation, survival, migration, senescence, autophagy and angiogenesis. They have been implicated in a range of disorders including malignant, metabolic, neurological and immune diseases. A more complete understanding of their cellular roles may lead to the development of novel IGFBP-based therapeutic opportunities.Page 2 of 51 3The somatomedin hypothesis, which postulated that growth hormone activity was mediated by a 1 serum factor, was published in 1957 (Salmon and Daughaday 1957). In the 1960s, several 2 circulating somatomedin activities were identified and attributed to peptides sized 5~8 kDa that had 3 both growth promoting and insulin-like metabolic effects. A paradox of these early observations 4 was that normoglycaemia was maintained in vivo despite the circulating concentrations of 5 somatomedins being sufficient to cause profound hypoglycaemia. Following the purification of 6 these small somatomedin peptides, it was observed that almost all of the circulating somatomedin 7 activity was found in a number of chromatographic peaks with apparent molecular weights greater 8 than 30~40 kDa and further studies indicated that this was due to binding by plasma binding 9proteins (Hintz and Liu 1977;Megyesi, et al. 1975;Zapf, et al. 1975). The apparent hypoglycaemia 10 paradox could then be resolved if somatomedin activity was inhibited by association with these 11 binding proteins. Of note, these early studies already demonstrated that insulin did not bind to these 12 proteins. 13 14In the following years, the somatomedin activities were identified as IGF-I and IGF-II, and they 15 were sequenced and cloned. IGF binding proteins (IGFBPs) 1-3 were the first to be identified and 16 purified, with IGFBPs 4-6 being subsequently described (Rajaram, et al. 1997;Rechler 1993). By 17 the early 1990s, all six members of this high affinity IGFBP family had been cloned and a number 18 of key structural and sequence similarities identified. Addition...

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Insulin-Like Growth Factor (IGF) Binding Protein-3 Attenuates Prostate Tumor Growth by IGF-Dependent and IGF-Independent Mechanisms

Cited by 78 publications

References 36 publications

Insulin-like growth factor binding protein-3 (IGFBP-3) acts as an invasion-metastasis suppressor in ovarian endometrioid carcinoma

Insulin-like growth factor binding protein-3 (IGFBP-3) acts as an invasion-metastasis suppressor in ovarian endometrioid carcinoma

Novel mechanism of IGF-binding protein-3 action on prostate cancer cells: inhibition of proliferation, adhesion, and motility

40 YEARS OF IGF1: IGF-binding proteins

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