S100B promotes the proliferation, migration and invasion of specific brain metastatic lung adenocarcinoma cell line

Jiang, Weifeng; Jia, Qianxin; Liu, Li‐Li; Zhao, Xinwen; Tan, Aixing; Ma, Ning; Zhang, Helong

doi:10.1002/cbf.1791

Cited by 17 publications

(16 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In glioma, serum S100ß has been suggested to be a predictive and prognostic factor, but these results have not been confirmed in other studies . S100ß could be involved in BM formation by promoting cell proliferation, cell migration and invasion and preventing apoptosis, as suggested in a study using a specific brain metastatic lung carcinoma cell‐line . However, as in our study, serum S100ß levels were not associated with BM in a series of 101 patients with BC .…”

Section: Discussioncontrasting

confidence: 94%

Serum NSE, MMP‐9 and HER2 extracellular domain are associated with brain metastases in metastatic breast cancer patients: predictive biomarkers for brain metastases?

Darlix

Lamy

Lopez-Crapez

et al. 2016

Intl Journal of Cancer

View full text Add to dashboard Cite

Breast cancer (BC) is the second most common cause of brain metastases (BM). Predictive factors for BM have been widely studied in metastatic BC; however, there is no known serum tumor marker to accurately predict BM. Elevated serum S100ß protein and neuron-specific enolase (NSE) could reflect the brain damages induced by BM. Matrix metalloproteinase 9 (MMP-9) is involved in tumor invasion and metastatic dissemination, including BM. Also, HER2-amplified BC were shown to have a particular tropism for central nervous system (CNS). This study evaluated the correlation of these biomarkers with the presence of BM in metastatic BC patients. In this case-control study, 88 consecutive metastatic BC patients with BM (BM group) treated in our institution (2008-2015) were retrospectively selected, based on the availability of frozen serum samples for tumor marker determination. Patients were matched by age, tumor biology and number of previous metastatic chemotherapy lines to 162 metastatic BC patients without CNS involvement (control group). Serum NSE, MMP-9 and HER2 extracellular domain (ECD) levels were significantly higher in the BM group (p = 0.0051, p = 0.0062 and p = 0.0057, respectively). In multivariate analysis, serum HER2 and MMP-9 levels accurately discriminated patients with BM: odds ratios 4.4 (p < 0.001; 95%CI: 1.9-9.6) for HER2 ECD and 3.5 (p = 0.005; 95%CI: 1.5-8.4) for MMP-9. In multivariate analysis, HER2 ECD and NSE serum levels were independent prognostic factors in patients with BM. Serum HER2 ECD and MMP-9 appear to be associated with BM in metastatic BC patients. Their predictive value for BM still needs to be evaluated in further prospective studies.

show abstract

Section: Discussioncontrasting

confidence: 94%

Serum NSE, MMP‐9 and HER2 extracellular domain are associated with brain metastases in metastatic breast cancer patients: predictive biomarkers for brain metastases?

Darlix

Lamy

Lopez-Crapez

et al. 2016

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…That implied PRCKA expression was associated with BM in NSCLC and the expression of the other four proteins was not. The former agreed with the reported results (25), but the latter did not (26,(30)(31)(32). The possible reasons are that previous studies examined mechanisms in vitro (26,31) or used cases with insufficient numbers (30,32), so the results require further study.…”

Section: Discussionsupporting

confidence: 81%

“…The results of previous studies reported that these five proteins were associated with BM in NSCLC (25,26,(30)(31)(32). As tumor invasion and metastasis are regulated with complicated networks, the proteins above are only isolated molecules of regulatory networks, and their expression is unavoidably regulated by upstream genes.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, this study collected a large number of characteristic clinical cases, and miRNA-328 and miRNA-378 were chosen as molecular markers to assess their prediction value for BM in NSCLC. In addition, their potential mechanisms were explored by investigating the expression of N-cadherin, E-cadherin, VEGF, PRKCA and S100B, which were reportedly associated with BM in NSCLC (25,26,(30)(31)(32), and VEGF and PRKCA were especially considered to mediate miRNA-378 and miRNA-328 mechanisms for BM in vitro (25,26). We expected this study could help to identify the predictive value of miRNA-328 and miRNA-378 for BM in NSCLC to provide some clinical guidelines for PCI in patients with NSCLC.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The predictive value and potential mechanisms of miRNA-328 and miRNA-378 for brain metastases in operable and advanced non-small-cell lung cancer

Sun

et al. 2015

Japanese Journal of Clinical Oncology

View full text Add to dashboard Cite

Objective: The incidence of brain metastases greatly varies in patients with non-small-cell lung cancer, and molecular markers are considered to predict brain metastases. Therefore, this study sought to identify the predictive value and potential mechanisms of miRNA-328 and miRNA-378 for brain metastases in non-small-cell lung cancer. Methods: Patients who received a curable surgery for their lung cancer were screened according to our criteria. Formalin-fixed paraffin-embedded samples from the patients were examined for the expression of miRNA-328 and miRNA-378 using real-time polymerase chain reaction and the expression of N-cadherin, E-cadherin, vascular endothelial growth factor, protein kinase Cα and S100B were investigated using immunohistochemical staining. Results: In total, 86 patients were screened for this study and 23 patients were diagnosed with brain metastases during the follow-up period. Comparing patients with and without brain metastases, the expression of miRNA-328 and miRNA-378 in tumor tissues were significantly different (P = 6.2 × 10 −5 and P = 2.8 × 10 −5 , respectively). For the patients with brain metastases, the expression of miRNA-328and miRNA-378 in tumor tissues compared with para-carcinoma tissues were also significantly different (P = 2.2 × 10 −5 and P = 1.6 × 10 −5 , respectively). For patients with brain metastases, the association between miRNA-328 and protein kinase Cα was significant (r = 0.591, P = 0.003), but that between miRNA-378 and protein kinase Cα was not significant (r = 0.259, P = 0.232). Conclusions:The expression of miRNA-328 and miRNA-378 in tumor tissues can be used to predict brain metastases in patients with non-small-cell lung cancer. miRNA-328 might promote brain metastases by regulating the expression of protein kinase Cα. However, the mechanisms of miRNA-378 to promote brain metastases should be studied in the future.

show abstract

“…Knockdown of S100B in many melanoma and other cancer cells have been studied before 24,39,40 . Based on these studies, S100B has been established as a legitimate drug target.…”

Section: Resultsmentioning

confidence: 99%

Simultaneous inhibition of key growth pathways in melanoma cells and tumor regression by a designed bidentate constrained helical peptide

et al. 2014

View full text Add to dashboard Cite

Protein-protein interactions are part of a large number of signaling networks and potential targets for drug development. However, discovering molecules that can specifically inhibit such interactions is a major challenge. S100B, a calcium-regulated protein, plays a crucial role in the proliferation of melanoma cells through protein-protein interactions. In this article, we report the design and development of a bidentate conformationally constrained peptide against dimeric S100B based on a natural tight binding peptide, TRTK-12. The helical conformation of the peptide was constrained by substitution of α-amino isobutyric acid----an amino acid having high helical propensity----in positions which do not interact with S100B. A branched bidentate version of the peptide, bound to S100B tightly with a dissociation constant of 8 nM. When conjugated to a cell penetrating peptide, it caused growth inhibition and rapid apoptosis in melanoma cells. The molecule exerts anti-proliferative action through simultaneous inhibition of key growth pathways including reactivation of wild-type p53 and inhibition of Akt and STAT-3 phosphorylation. The apoptosis induced by the bidentate constrained helix is caused by direct migration of p53 to mitochondria. At moderate intravenous dose, the peptide completely inhibits melanoma growth in a mouse model without any significant observable toxicity. The specificity was shown by lack of ability of a double mutant peptide to cause tumor regression at the same dose level. The methodology described here for direct protein-protein interaction inhibition may be effective for rapid development of inhibitors against relatively weak protein-protein interactions for de novo drug development.

show abstract

S100B promotes the proliferation, migration and invasion of specific brain metastatic lung adenocarcinoma cell line

Cited by 17 publications

References 25 publications

Serum NSE, MMP‐9 and HER2 extracellular domain are associated with brain metastases in metastatic breast cancer patients: predictive biomarkers for brain metastases?

Serum NSE, MMP‐9 and HER2 extracellular domain are associated with brain metastases in metastatic breast cancer patients: predictive biomarkers for brain metastases?

The predictive value and potential mechanisms of miRNA-328 and miRNA-378 for brain metastases in operable and advanced non-small-cell lung cancer

Simultaneous inhibition of key growth pathways in melanoma cells and tumor regression by a designed bidentate constrained helical peptide

Contact Info

Product

Resources

About