Inhibition of functional HER family members increases the sensitivity to docetaxel in human ovarian cancer cell lines

Bijman, Marcel N.A.; Berkel, Maria P.A. van; Kok, Mirjam; Janmaat, Maarten L.; Boven, Epie

doi:10.1097/cad.0b013e32832afc24

Cited by 27 publications

(17 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These cell lines have different levels of HER1 and HER2 expression. Several studies have shown that both epithermal growth factor 1 and 2 are associated and expressed at high levels in human ovarian cancer cell line SKOV3 and human non-small cell line cancer A549 but have lower expression of HER1 and HER2, respectively [17, 35, 36]. HER2 has important role in proliferation and progression of a variety of cancers such as breast, ovarian, non-small cell lung and hepatoma [37].…”

Section: Discussionmentioning

confidence: 99%

99mTc-radiolabeled GE11-modified peptide for ovarian tumor targeting

et al. 2017

View full text Add to dashboard Cite

BackgroundOvarian cancer is a serious threat for women health and the early diagnosis of this cancer might improves the survival rate of patients. The use of the targeted radiopharmaceuticals could be a non-invasive and logical method for tumor imaging. The aim of this study was to radiolabel GE11 peptide as a new specific probe for imaging of ovarian tumor.MethodsHYNIC-SSS-GE11 peptide was labeled with 99mTc using tricine as a coligand. The 99mTc-tricine-HYNIC-SSS-GE11 peptide was evaluated for specific cellular binding in three cell lines with different levels of EGFR expression. Tumor targeting was assessed in SKOV3 tumor bearing mice.ResultsBy using tricine as a coligand, labeling yield was more than 98% and the stability of the radiolabelled peptide in human serum up to 4 h was 96%. The in vitro cell uptake test showed that this radiolabeled peptide had a good affinity to SKOV3 cells with dissociation constant of 73 nM. The in vivo results showed a tumor/muscle ratio of 3.2 at 4 h following injection of 99mTc-tricine-HYNIC-SSS-GE11 peptide.ConclusionsResults of this study showed that 99mTc-tricine-HYNIC-SSS-GE11 peptide could be a promising tool for diagnosis and staging of ovarian cancer.Graphical Abstract 99mTc-tricine-HYNIC-SSS-GE11, a novl targeted agent for ovarian tumor imaging

show abstract

Section: Discussionmentioning

confidence: 99%

99mTc-radiolabeled GE11-modified peptide for ovarian tumor targeting

et al. 2017

View full text Add to dashboard Cite

show abstract

“…As example, cetuximab, an EGFR-directed monoclonal antibody, inhibited cell growth in OVCAR-3 cells, whereas SKOV-3 cell growth was not significantly affected 15. The MAPK signaling pathway including Erk, SAPK/JNK and p38 MAPK has been well characterized and plays an important role in the regulation of proliferation, survival and apoptosis in response to external stimuli in ovarian cancer 16.…”

Section: Discussionmentioning

confidence: 99%

Preferential Effect of Akt2-Dependent Signaling on the Cellular Viability of Ovarian Cancer Cells in Response to EGF

Khabele¹,

Kabir²,

Dong³

et al. 2014

J. Cancer

View full text Add to dashboard Cite

Objective: Overexpression of the epidermal growth factor receptor (EGFR) is associated with the malignant phenotype in many cancers including ovarian cancer, which leads to increased cell proliferation and survival. In spite of emerging EGFR inhibitors as a potentially useful agent, they are largely ineffective in patients with advanced or recurrent ovarian cancers. Since Akt as a key downstream factor of EGFR is highly activated in some high grade serous ovarian tumors, the augmented Akt activation may attribute to irregular EGFR-mediated signaling observed in ovarian cancer. Here we investigated the differential effect of Akt on the EGF-induced cell viability in a panel of ovarian cancer cell lines.Methods: Cellular viability assay and western blot analysis were used to measure cell viability and expression levels of proteins, respectively. Knockdown of Akt was achieved with siRNA and stable transfection of expression vectors was performed.Results: Cellular viability increased in OVCAR-3 ovarian cancer cells exposed to EGF, but little to no difference was observed in the 5 other ovarian cancer cells including SKOV-3 cells despite of the expression of EGFR. In OVCAR-3 cells, EGF activated Erk and Akt, but an Erk inhibitor had no impact on cellular viability. On the other hand, the EGFR and PI3K inhibitors decreased EGF-induced cellular viability, indicating the involvement of Akt signaling. Although EGF activated Erk in SKOV-3 cells, the Akt activation was very weak as compared to OVCAR-3 cells. Furthermore, we observed a different expression of Akt isoforms: Akt1 was constitutively expressed in all tested ovarian cancer cells, while Akt3 was little expressed. Interestingly, Akt2 was highly expressed in OVCAR-3 cells. Knockdown of Akt2 blocked EGF-induced OVCAR-3 cell viability whereas knockdown for Akt1 and Erk1/2 had no significant effect. Stable transfection of Akt2 into SKOV-3 cells phosphorylated more Akt and enhanced cell viability in response to EGF.Conclusions: Akt2-dependent signaling appears to play an important role in EGFR-mediated cellular viability in ovarian cancer and targeting specific Akt isoform may provide a potential therapeutic approach for EGFR-expressing ovarian cancers.

show abstract

“…Likewise, it has recently been proposed that an autocrine loop involving NRG1 and an activated ErbB-3 drives progression of a subset of ovarian tumors (Sheng et al , 2010). Importantly, ErbB receptors and their ligands are also involved in resistance to endocrine and cytotoxic therapy, as well as to radiotherapy (Bijman et al , 2009; Freeman et al , 2009). …”

Section: Introductionmentioning

confidence: 99%

“…In the same vein, human breast cancer cells selected in vivo for resistance to trastuzumab remarkably overexpress EGFR and specific ErbB ligands (Ritter et al , 2007). Likewise, EGFR- and ErbB-2-targeting monoclonal antibodies increase the antitumor effects of docetaxel by blocking functional receptors and drug evasion mechanisms (Bijman et al , 2009; Freeman et al , 2009). …”

Section: Introductionmentioning

confidence: 99%

A recombinant decoy comprising EGFR and ErbB-4 inhibits tumor growth and metastasis

et al. 2011

View full text Add to dashboard Cite

EGF-like growth factors control tumor progression, as well as evasion from the toxic effects of chemotherapy. Accordingly, antibodies targeting the cognate receptors, such as EGFR/ErbB-1 and the co-receptor HER2/ErbB-2, are widely used to treat cancer patients, but agents that target the EGF-like growth factors are not available. To circumvent the existence of 11 distinct ErbB ligands, we constructed a soluble fusion protein (hereinafter: TRAP-Fc) comprising truncated extracellular domains of EGFR/ErbB-1 and ErbB-4. The recombinant TRAP-Fc retained high affinity ligand binding to EGF-like growth factors and partially inhibited growth of a variety of cultured tumor cells. Consistently, TRAP-Fc displayed an inhibitory effect in xenograft models of human cancer, as well as synergy with chemotherapy. Additionally, TRAP-Fc inhibited invasive growth of mammary tumor cells and reduced their metastatic seeding in the lungs of animals. Taken together, the activities displayed by TRAP-Fc reinforce critical roles of EGF-like growth factors in tumor progression, and they warrant further tests of TRAP-Fc in pre-clinical models.

show abstract

Inhibition of functional HER family members increases the sensitivity to docetaxel in human ovarian cancer cell lines

Cited by 27 publications

References 40 publications

99mTc-radiolabeled GE11-modified peptide for ovarian tumor targeting

99mTc-radiolabeled GE11-modified peptide for ovarian tumor targeting

Preferential Effect of Akt2-Dependent Signaling on the Cellular Viability of Ovarian Cancer Cells in Response to EGF

A recombinant decoy comprising EGFR and ErbB-4 inhibits tumor growth and metastasis

Contact Info

Product

Resources

About