Delivery of miR-200c Mimic with Poly(amido amine) CXCR4 Antagonists for Combined Inhibition of Cholangiocarcinoma Cell Invasiveness

Xie, Ying; Wehrkamp, Cody J.; Li, Jing; Wang, Yan; Wang, Yazhe; Mott, Justin L.; Oupický, David

doi:10.1021/acs.molpharmaceut.5b00894

Cited by 26 publications

(20 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CXCR4 antagonists can inhibit migration of cancer cells that utilize the CXCR4/SDF1 axis and we have previously shown that PCX and their polyplexes inhibited CXCR4-mediated migration and invasion in human osteosarcoma and cholangiocarcinoma cells [30, 33, 51]. Here, we studied the migration of gemcitabine-treated CD18/HPAF.luc cells in a Boyden chamber using 10% serum as the chemotactic signal.…”

Section: Resultsmentioning

confidence: 99%

Polyplex-mediated inhibition of chemokine receptor CXCR4 and chromatin-remodeling enzyme NCOA3 impedes pancreatic cancer progression and metastasis

et al. 2016

Self Cite

View full text Add to dashboard Cite

Pancreatic cancer (PC) is one of the most aggressive malignancies due to intense desmoplasia, extreme hypoxia and inherent chemoresistance. Studies have implicated the expression of chemokine receptor CXCR4 and nuclear receptor co-activator-3 (NCOA3) in the development of desmoplasia and metastatic spread of PC. Using a series of polymeric CXCR4 antagonists (PCX), we optimized formulation of PCX/siNCOA3 polyplexes to simultaneously target CXCR4 and NCOA3 in PC. Cholesterol-modified PCX showed maximum CXCR4 antagonism, NCOA3 silencing and inhibition of PC cell migration in vitro. The optimized PCX/siNCOA3 polyplexes were used in evaluating antitumor and antimetastatic activity in orthotopic mouse model of metastatic PC. The polyplexes displayed significant inhibition of primary tumor growth, which was accompanied by a decrease in tumor necrosis and increased tumor perfusion. The polyplexes also showed significant antimetastatic effect and effective suppression of metastasis to distant organs. Overall, dual-function PCX/siNCOA3 polyplexes can effectively regulate tumor microenvironment to decrease progression and dissemination of PC.

show abstract

Section: Resultsmentioning

confidence: 99%

Polyplex-mediated inhibition of chemokine receptor CXCR4 and chromatin-remodeling enzyme NCOA3 impedes pancreatic cancer progression and metastasis

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…Therefore, it is necessary to identify and employ novel biomarkers as possible therapeutic targets or prognostic predictors, which will be used as an adjunct to the staging system and contribute to the optimization of treatment for patients with NSCLC. miRNAs as a recent focus in tumor research serve an oncogenic or tumor-suppressive role in different cancer types via various pathways (17)(18)(19). miR-200c is a member of the miR-200 family, which is located on chromosome 12p13 and is closely associated with carcinogenesis and disease progression in a wide range of cancer types (20,21).…”

Section: Discussionmentioning

confidence: 99%

Potential use of microRNA-200c as a prognostic marker in non-small cell lung cancer

Tian

Yue

et al. 2017

Oncology Letters

View full text Add to dashboard Cite

Abstract. MicroRNAs (miRNAs/miRs) are a class of small, highly conserved non-coding RNAs that can serve either oncogenic or tumor-suppressive roles in a wide variety of tumors. miR-200c is a member of the miR-200 family whose specific role in non-small cell lung cancer (NSCLC) has not yet been elucidated. The purpose of the present study was to detect the expression level of miR-200c in NSCLC, and to analyze its association with clinicopathological factors and patient prognosis. The present study determined the expression levels of miR-200c in 110 tumor samples collected from patients diagnosed with NSCLC who underwent complete tumor resection with regional lymph node dissection, as assessed by reverse transcription-quantitative polymerase chain reaction. The association between the expression level of miR-200c and clinicopathological features and patient prognosis was also analyzed. The results showed that miR-200c overexpression was detected in 66 of the 110 cases and was significantly associated with positive lymph node metastasis (P<0.001). Univariate survival analysis demonstrated that high miR-200c expression, positive lymph node metastasis and advanced Tumor-Node-Metastasis (TNM) classification stage significantly predicted decreased 5-year disease-free survival rates (all P<0.05) and poor 5-year overall survival rates (all P<0.01), respectively. The results of multivariate Cox regression analysis showed that TNM stage and miR-200c expression retained its significance as an independent prognostic factor for unfavorable 5-year disease-free survival rates (P<0.05) and poor 5-year overall survival rates (P<0.01). The present findings suggest that miR-200c overexpression is significantly associated with poor survival rates in NSCLC and that miR-200c could play an oncogenic role. miR-200c may have clinical potential as a promising prognostic predictor for patients with NSCLC.

show abstract

“…FTY720, a synthetic sphingosine immunosuppressant, inhibits EMT and favors reversion of EMT that is called MET (mesenchymal-epithelial transition) in CCA cells and, prevents metastasis in vivo after implantation of CCA cells into the peritoneal cavity of immunocompromised mice [146]. Recently, taking advantage of the presence of CXCR4 at the surface of CCA cells, a polymeric CXCR4 antagonist capable of delivering miR-200c has been developed to inhibit EMT inducer ZEB1 in CCA cells [147]. miR-200c was chosen as a potential treatment for its ability to target ZEB1.…”

Section: Targeting Emt Pathwaysmentioning

confidence: 99%

Epithelial-mesenchymal transition in cholangiocarcinoma: From clinical evidence to regulatory networks

Vaquero

Guedj

Clapéron

et al. 2017

Journal of Hepatology

113

122

View full text Add to dashboard Cite

Cholangiocarcinoma (CCA) is an aggressive tumor with a poor prognosis due to its late clinical presentation and the lack of effective non-surgical therapies. Unfortunately, most of the patients are not eligible for curative surgery owing to the presence of metastases at the time of diagnosis. Therefore, it is important to understand the steps leading to cell dissemination in patients with CCA. To metastasize from the primary site, cancer cells must acquire migratory and invasive properties by a cell plasticity-promoting phenomenon known as epithelial-mesenchymal transition (EMT). EMT is a reversible dynamic process by which epithelial cells gradually adopt structural and functional characteristics of mesenchymal cells, and has lately become a center of attention in the field of metastatic dissemination. In the present review, we aim to provide an extensive overview of the current clinical data and the prognostic value of different EMT markers that have been analyzed in CCA. We summarize all the regulatory networks implicated in EMT from the membrane receptors to the main EMT-inducing transcription factors (SNAIL, TWIST and ZEB). Furthermore, since a tumor is a complex structure not exclusively formed by tumor cells, we also address the prominent role of the main cell types of the desmoplastic stroma that characterizes CCA in the regulation of EMT. Finally, we discuss the therapeutic considerations and difficulties faced to develop an effective anti-EMT treatment due to the redundancies and bypasses among the pathways regulating EMT. 4Key Point Box -EMT is an early event of metastasis that endows tumor cells with invasive properties enabling them to spread toward other territories.-EMT contributes to CCA progression and chemoresistance.-The three families of transcription factors that regulate epithelial and mesenchymal marker expression during EMT (SNAIL, TWIST and ZEB) contribute to CCA progression.-Cells of CCA microenvironment, and not only cancer cells, lead to the activation of EMT.

show abstract

Delivery of miR-200c Mimic with Poly(amido amine) CXCR4 Antagonists for Combined Inhibition of Cholangiocarcinoma Cell Invasiveness

Cited by 26 publications

References 44 publications

Polyplex-mediated inhibition of chemokine receptor CXCR4 and chromatin-remodeling enzyme NCOA3 impedes pancreatic cancer progression and metastasis

Polyplex-mediated inhibition of chemokine receptor CXCR4 and chromatin-remodeling enzyme NCOA3 impedes pancreatic cancer progression and metastasis

Potential use of microRNA-200c as a prognostic marker in non-small cell lung cancer

Epithelial-mesenchymal transition in cholangiocarcinoma: From clinical evidence to regulatory networks

Contact Info

Product

Resources

About