Targeting the insulin-like growth factor-1 receptor by picropodophyllin as a treatment option for glioblastoma

Yin, Shucheng; Girnita, Ada; Strömberg, Thomas; Khan, Zahidul; Andersson, Sandra; Zheng, Huiyuan; Ericsson, Christer; Axelson, Magnus; Nistér, Monica; Larsson, Olle; Ekström, Tomas J.; Girnita, Leonard

doi:10.1093/neuonc/nop008

Cited by 81 publications

(94 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…I-OMe-Tyrphostin AG 538 is an insulin growth factor 1 (IGF-1) receptor (IGF-1R) protein tyrosine kinase inhibitor. IGF-1 has been well discussed in GBM (13), and targeting IGF-1R has been studied as a treatment option for GBM (14). (-)-Perillic acid is a metabolite of perillyl alcohol (POH), which has shown a therapeutic anticancer effect and is currently under phase I and II clinical trials for human cancers including GBM (15,16).…”

Section: Discussionmentioning

confidence: 99%

Identification of novel small-molecule inhibitors of glioblastoma cell growth and invasion by high-throughput screening

et al. 2012

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Identification of novel small-molecule inhibitors of glioblastoma cell growth and invasion by high-throughput screening

et al. 2012

View full text Add to dashboard Cite

“…[96,97] Therefore, IGF-1R tyrosine kinase inhibitors or IGF-1 inhibitors, such as osthole, have been used to inhibit GBM proliferation, migration and EMT. [97,98] In a recent study of 218 cases of human GBM, IGF-1R overexpression was reported as an independent prognostic factor associated with shorter survival time and a less favorable response to temozolomide. [99] C-MET expression levels correlate with tumor grade in CNS malignancies, [100] and its activation also mediates EMTpromoting signals in cancer cells via class I A PI3K.…”

Section: Emt Cell Invasion and Motilitymentioning

confidence: 99%

The role of the PI3K/AKT/mTOR pathway in brain tumor metastasis

Crespo¹,

Kind²,

Arcaro³

2016

JCMT

View full text Add to dashboard Cite

The PI3K/AKT/mTOR (PAM) pathway is involved in a variety of cellular functions and often contributes to oncogenesis and cancer progression. It has been recognized that this pathway is frequently activated in the most common central nervous system cancers of adults and children, malignant gliomas and medulloblastomas (MB). In these tumors, the PAM network controls key functions necessary for cell invasion and metastasis, such as cell motility. This review summarizes the current knowledge about the role of PAM signaling in cell invasion and metastasis in gliomas and MB. Current approaches to inhibit cell invasion and metastasis by targeting the PAM pathway will also be discussed.

show abstract

“…(26) Inhibition of IGF-1R with PPP has been demonstrated in multiple myeloma, (23) breast cancer, (27) melanoma (28) and glioblastoma cells. (29) Although IGF-1R and the stimulatory ligands (IGF and insulin) are important for cancer proliferation, anti-IGF-1R therapy has not shown enough clinical benefits in randomized phase III trials. (30) The mediation of IGF-1R signaling in cancer cell is still unclear.…”

mentioning

confidence: 99%

Heterogeneity of neuroblastoma cell lines in insulin‐like growth factor 1 receptor/Akt pathway‐mediated cell proliferative responses

et al. 2013

View full text Add to dashboard Cite

Insulin-like growth factor 1 receptor (IGF-1R) is critical for cancer cell proliferation; however, recent clinical anti-IGF-1R trials did not show clear clinical benefit in cancer therapy. We hypothesized that IGF-1R signaling-mediated proliferative response is heterogeneous in neuroblastoma (NB) cells, and analyzed the cell growth of 31 NB cell lines cultured in three different media, including Hybridoma-SFM medium (with insulin) and RPMI1640 with ⁄ without 10% FBS. Three growth patterns were found. In response to IGF and insulin, cell proliferation and Akt phosphorylation were upregulated in 13 cell lines, and suppressed by MK2206 (Akt inhibitor) and picropodophyllin (IGF-1R inhibitor). Interestingly, 3 of these 13 cell lines showed Akt self-phosphorylation and cell proliferation in RPMI1640; their proliferation was downregulated by anti-IGF-1 or anti-IGF-2 neutralizing antibody, suggesting the existence of an autocrine loop in the IGF-1R ⁄ Akt pathway. Eighteen NB cell lines did not proliferate in RPMI1640, even though Akt phosphorylation was upregulated by IGF and insulin. Based on the heterogeneous response of the IGF-1R ⁄ Akt pathway, the 31 NB cell lines could be classified into group 1 (autocrine IGF-mediated), group 2 (exogenous IGF-mediated) and group 3 (partially exogenous IGF-mediated) NB cell lines. In addition, group 3 NB cell lines were different from group 1 and 2, in terms of serum starvation-induced caspase 3 cleavage and picropodophyllin-induced G2 ⁄ M arrest. These results indicate that the response of the IGF-1R ⁄ Akt pathway is an important determinant of the sensitivity to IGF-1R antagonists in NB. To our knowledge, this is the first report describing heterogeneity in the IGF-1R ⁄ Aktmediated proliferation of NB cells. (Cancer Sci 2013; 104: 1162-1171 N euroblastoma (NB), a malignant tumor that originates from the sympathetic nervous system, is one of the most frequent pediatric solid tumors.(1) NB is characterized by heterogeneous clinical behaviors, tumor invasiveness being different according to age and anatomic stage at diagnosis. The tumor is sometimes completely curable and may even regress spontaneously, especially in younger children.(2) Heterogeneity of the tumors depends on the degree of morphological differentiation and on histopathology. Insulin and insulin-like growth factors (IGF, including IGF-1 and 2) belong to a family of mitogenic growth factors. IGF, insulin, and their receptors are involved in normal growth and differentiation of most tissues. The biological actions of both IGF and insulin can be mediated by the IGF-1 receptor (IGF-1R), a transmembrane heterotetramer, which is involved in mitogenic, anti-apoptotic and oncogenic transforming responses.(4,5) The functional IGF-1R contains two extracellular a-subunits and two intracellular b-subunits that form a heterotetrameric complex. The structural homology of IGF-1R and insulin receptor (IR) allows formation of hybrid receptors (hybrid-R) in which an IGF-1R chain is connected to an IR chain. Ligand interaction with a-...

show abstract

Targeting the insulin-like growth factor-1 receptor by picropodophyllin as a treatment option for glioblastoma

Cited by 81 publications

References 28 publications

Identification of novel small-molecule inhibitors of glioblastoma cell growth and invasion by high-throughput screening

Identification of novel small-molecule inhibitors of glioblastoma cell growth and invasion by high-throughput screening

The role of the PI3K/AKT/mTOR pathway in brain tumor metastasis

Heterogeneity of neuroblastoma cell lines in insulin‐like growth factor 1 receptor/Akt pathway‐mediated cell proliferative responses

Contact Info

Product

Resources

About