Biological effects induced by insulin‐like growth factor binding protein 3 (IGFBP‐3) in malignant melanoma

Øy, Geir Frode; Slipicevic, Ana; Davidson, Ben; Faye, Ragnar S.; Mælandsmo, Gunhild M.; Flørenes, Viví Ann

doi:10.1002/ijc.24727

Cited by 20 publications

(12 citation statements)

References 48 publications

(93 reference statements)

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“…Because growing evidence has indicated that IGFBP3 is involved in the development of various cancers, including colon cancer, breast cancer, and malignant melanoma, 13 , 14 , 24 we also investigated IGFBP3 expression in surgically obtained specimens from patients with CSCC. The results of our immunohistochemistry assays indicated that brown signal representing IGFBP3 protein was markedly stronger in the cells of CSCC tissue than that in the cells of normal skin tissue ( Figure 2C–D ).…”

Section: Resultsmentioning

confidence: 99%

“… 22 , 23 However, other studies have shown that IGFBP3 has dual functional effects on apoptosis and proliferation in malignant melanoma and astrocytoma. 24 , 25 Consequently, the role of IGFBP3 in tumor development is complex and controversial and has thus become the focus of recent research. 24 At present, little is known regarding its role in CSCC.…”

Section: Introductionmentioning

confidence: 99%

“… 24 , 25 Consequently, the role of IGFBP3 in tumor development is complex and controversial and has thus become the focus of recent research. 24 At present, little is known regarding its role in CSCC.…”

Section: Introductionmentioning

confidence: 99%

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Effects of insulin-like growth factor binding protein 3 on apoptosis of cutaneous squamous cell carcinoma cells

Liu

Guo

Huang

et al. 2018

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BackgroundCutaneous squamous cell carcinoma (CSCC) is the second most common carcinoma worldwide. Clinical treatment for patients with CSCC remains non-ideal. Insulin-like growth factor binding protein 3 (IGFBP3), a member of the insulin-like growth (IGF) system, participates in several biological processes, including cellular proliferation and apoptosis. Here, we explored the functional role of IGFBP3 in apoptosis and proliferation of A431 cells, a human CSCC cell line.Materials and methodsDifferential expression analysis, immunohistochemistry, immunoblotting, TUNEL assay, and CCK8 assay techniques were used to investigate the IGFBP3 expression levels in both A431 cells and CSCC tissue surgically obtained from humans as well as to explore the functional role of IGFBP3 in the apoptosis and proliferation of A431 cells.ResultsBy using normal epidermal keratinocytes for comparison, we identified the top 10 ranked differentially upregulated genes expressed in human cutaneous squamous cell carcinoma cell lines. Among these 10 genes, IGFBP3 was ranked number 1. By using immunohistochemistry, we found that the expression level of IGFBP3 was significantly elevated in CSCC tissue compared with that in normal human skin tissue. Knockdown of IGFBP3 in A431 cells by transfection with IGFBP3-specific siRNA markedly altered the expression of proteins that contribute to apoptosis via mitochondrial pathways, significantly suppressing the expression of Bax and active caspase-3, while significantly increasing B-cell lymphoma-2 expression. TUNEL assay confirmed the effect of knockdown of IGFBP3 on the apoptosis as well. In addition, knockdown of IGFBP3 inhibited the proliferation of A431 cells.ConclusionIGFBP3 is overexpressed in both CSCC cell lines and tissue. Knockdown of IGFBP3 enhanced the apoptosis via a mitochondrial pathway and inhibited the proliferation of A431 cells. These findings indicate that IGFBP3 may be a biomarker and a potential therapeutic target for CSCC.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effects of insulin-like growth factor binding protein 3 on apoptosis of cutaneous squamous cell carcinoma cells

Liu

Guo

Huang

et al. 2018

OTT

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“…In addition, the combination of elevated IGF-1-R and IGFBP-3 had the shortest time to progression in these patients (31). Elevated levels of IGFBP-3 have also been reported in metastatic melanoma and targeted silencing of IGFBP-3 expression through siRNA lead to a reduction in proliferation (32). This suggests that elevated IGFBP-3 contributes to increased proliferation in late stages of cancer development.…”

Section: Impact Of Igf Signaling On Head and Neck Cancersmentioning

confidence: 99%

Impact of targeting insulin-like growth factor signaling in head and neck cancers

Limesand

Chibly

Fribley

2013

Growth Hormone & IGF Research

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The IGF system has been shown to have either negative or negligible impact on clinical outcomes of tumor development depending on specific tumor sites or stages. This review focuses on the clinical impact of IGF signaling in head and neck cancer, effects of IGF targeted therapies, and the multi-dimensional role of IRS 1/2 signaling as a potential mechanism in resistance to targeted therapies. Similar to other tumor sites, both negative and positive correlations between levels of IGF-1/IGF-1-R and clinical outcomes in head and neck cancer have been reported. In addition, utilization of IGF targeted therapies has not demonstrated significant clinical benefit; therefore the prognostic impact of the IGF system on head and neck cancer remains uncertain.

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“…IGFBP3 was more strongly expressed in metastatic and cutaneous melanoma compared to melanocytes [33]. Its function seems to depend on the cellular context, as both anti- and pro-tumorigenic roles were attributed to this protein [34,35]. …”

Section: Discussionmentioning

confidence: 99%

Gene expression analysis after receptor tyrosine kinase activation reveals new potential melanoma proteins

et al. 2010

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BackgroundMelanoma is an aggressive tumor with increasing incidence. To develop accurate prognostic markers and targeted therapies, changes leading to malignant transformation of melanocytes need to be understood. In the Xiphophorus melanoma model system, a mutated version of the EGF receptor Xmrk (Xiphophorus melanoma receptor kinase) triggers melanomagenesis. Cellular events downstream of Xmrk, such as the activation of Akt, Ras, B-Raf or Stat5, were also shown to play a role in human melanomagenesis. This makes the elucidation of Xmrk downstream targets a useful method for identifying processes involved in melanoma formation.MethodsHere, we analyzed Xmrk-induced gene expression using a microarray approach. Several highly expressed genes were confirmed by realtime PCR, and pathways responsible for their induction were revealed using small molecule inhibitors. The expression of these genes was also monitored in human melanoma cell lines, and the target gene FOSL1 was knocked down by siRNA. Proliferation and migration of siRNA-treated melanoma cell lines were then investigated.ResultsGenes with the strongest upregulation after receptor activation were FOS-like antigen 1 (Fosl1), early growth response 1 (Egr1), osteopontin (Opn), insulin-like growth factor binding protein 3 (Igfbp3), dual-specificity phosphatase 4 (Dusp4), and tumor-associated antigen L6 (Taal6). Interestingly, most genes were blocked in presence of a SRC kinase inhibitor. Importantly, we found that FOSL1, OPN, IGFBP3, DUSP4, and TAAL6 also exhibited increased expression levels in human melanoma cell lines compared to human melanocytes. Knockdown of FOSL1 in human melanoma cell lines reduced their proliferation and migration.ConclusionAltogether, the data show that the receptor tyrosine kinase Xmrk is a useful tool in the identification of target genes that are commonly expressed in Xmrk-transgenic melanocytes and melanoma cell lines. The identified molecules constitute new possible molecular players in melanoma development. Specifically, a role of FOSL1 in melanomagenic processes is demonstrated. These data are the basis for future detailed analyses of the investigated target genes.

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Biological effects induced by insulin‐like growth factor binding protein 3 (IGFBP‐3) in malignant melanoma

Cited by 20 publications

References 48 publications

Effects of insulin-like growth factor binding protein 3 on apoptosis of cutaneous squamous cell carcinoma cells

Effects of insulin-like growth factor binding protein 3 on apoptosis of cutaneous squamous cell carcinoma cells

Impact of targeting insulin-like growth factor signaling in head and neck cancers

Gene expression analysis after receptor tyrosine kinase activation reveals new potential melanoma proteins

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