SDF-1 and MMP2 cross talk in cancer cells and tumor microenvironment in non-small cell lung cancer

Osman, Nehad M.; Osman, Wesam M.

doi:10.1016/j.ejcdt.2016.01.001

Cited by 7 publications

(5 citation statements)

References 56 publications

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“…The breakdown of the ECM and basement membrane could permit cancer cells to spread to other tissues and organs. 35 , 36 , 37 To evaluate the MMP-2 expression, we performed the immunofluorescence staining on tumor tissues from nude mice treated with DGLA and 3WJ-EpCAM-D5D siRNA nanoparticle. The immunofluorescence images of tumor tissues indicated that the MMP-2 expression was suppressed by the treatment of DGLA and 3WJ-EpCAM-D5D siRNA nanoparticle ( Figure 5 B, p < 0.05).…”

Section: Resultsmentioning

confidence: 99%

EpCAM-Targeted 3WJ RNA Nanoparticle Harboring Delta-5-Desaturase siRNA Inhibited Lung Tumor Formation via DGLA Peroxidation

Pang

Shah

Wang

et al. 2020

Molecular Therapy - Nucleic Acids

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Knocking down delta-5-desaturase (D5D) expression by D5D small interfering RNA (siRNA) has been reported that could redirect the cyclooxygenase-2 (COX-2)-catalyzed dihomo-γ-linolenic acid (DGLA) peroxidation from producing prostaglandin E2 to 8-hydroxyoctanoic acid (8-HOA), resulting in the inhibition of colon and pancreatic cancers. However, the effect of D5D siRNA on lung cancer is still unknown. In this study, by incorporating epithelial cell adhesion molecule (EpCAM) aptamer and validated D5D siRNA into the innovative three-way junction (3WJ) RNA nanoparticle, target-specific accumulation and D5D knockdown were achieved in the lung cancer cell and mouse models. By promoting the 8-HOA formation from the COX-2-catalyzed DGLA peroxidation, the 3WJ-EpCAM-D5D siRNA nanoparticle inhibited lung cancer growth in vivo and in vitro . As a potential histone deacetylases inhibitor, 8-HOA subsequently inhibited cancer proliferation and induced apoptosis via suppressing YAP1/TAZ nuclear translocation and expression. Therefore, this 3WJ-RNA nanoparticle could improve the targeting and effectiveness of D5D siRNA in lung cancer therapy.

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Section: Resultsmentioning

confidence: 99%

EpCAM-Targeted 3WJ RNA Nanoparticle Harboring Delta-5-Desaturase siRNA Inhibited Lung Tumor Formation via DGLA Peroxidation

Pang

Shah

Wang

et al. 2020

Molecular Therapy - Nucleic Acids

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“…MMPs are typically expressed at moderate levels; their expression rapidly grows in response to tissue injury (8,14) and the course of inflammation processes or cancer development. It was previously reported that MMP2 immunoexpression was significantly higher in the lung cancer group than among the healthy control group (45).…”

Section: Mmp2 Expressed On Comparable Level In Both Tissuesmentioning

confidence: 99%

“…Elevated MMP2 expression was observed in stromal fibroblasts, preneoplastic bronchial squamous lesions and pulmonary carcinoma (both in highly invasive and moderate growth areas) (11)(12)(13). In NSCLC, the MMP2 upregulation has been associated with greater tumor size or distant metastasis (14,15). The MMPs' action can be specifically inhibited by non-covalent binding of TIMPs, which leads to tumor growth suppression and apoptosis promotion (9,16,17).…”

Section: Introductionmentioning

confidence: 99%

A Strong Decrease in TIMP3 Expression Mediated by the Presence of miR-17 and 20a Enables Extracellular Matrix Remodeling in the NSCLC Lesion Surroundings

et al. 2019

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Background: Lung cancer is one of the most common causes of death worldwide with a relatively high fatality rate and a mean 5-years survival of about 18%. One of the hallmarks of cancer is the extracellular matrix (ECM) remodeling, which is crucial for metastasis. This process may be regulated by miRs targeting metalloproteinases (MMPs) associated with the ECM breakdown and metastatic process or blocking the action of tissue inhibitors of metalloproteinases (TIMPs). Search for early biomarkers is essential in detecting non-small cell lung cancer (NSCLC) and distinguishing its subtypes: Adenocarcinoma (AC) from Squamous Cell Carcinoma (SCC), enabling targeted chemotherapy.Methods: MiR-17 and miR-20a targeting MMP2 and TIMP3 were selected by TCGA data analysis with further validation using miRTarBase and literature. The study group comprised 47 patients with primary NSCLC (AC and SCC subtypes). RNA was isolated from the tumor and normal-looking neighboring tissue (NLNT) free of cancer cells. MiRs from peripheral blood exosomes were extracted on admission and 5-7 days after surgery. Gene and miRs expression were assessed in qPCR using TaqMan probes. Results:The MMP2 has been expressed on a similar level in NLNT, as in cancer. While, TIMP3 expression was decreased both in cancer tissue and NLNT, with significantly lower expression in cancer. TIMP3 downregulation in NLNT and in SCC subtype correlated negatively with miR-20a. The preoperative miR-17 expression was significantly higher among patients with SCC compared to AC. Receiver operating characteristic (ROC) analysis of miR-17 as AC subtype classifier revealed 90% specificity and 48% sensitivity in optimal cut-off point with area under ROC curve (AUC): 0.71 (95%CI: 0.55-0.87). Within NSCLC subtypes: a strong negative correlation between pack-years (PY) and TIMP3 expression was observed for NLNT in the SCC group. Czarnecka et al. ECM Remodeling in NSCLC Conclusion:The TIMP3 silencing observed in the NLNT and its negative correlation with presurgical expression of miR-20a (from serum exosomes), suggest that miRs can influence ECM remodeling at a distance from the center of the lesion. The miRs expression pattern in serum obtained before surgery significantly differs between AC and SCC subtypes. Moreover, decreased TIMP3 expression in NLNT (in SCC group) negatively correlates with the amount of tobacco smoked in a lifetime in PY.Keywords: NSCLC molecular diagnostic markers, miRNA regulation, microRNA, extracellular matrix remodeling, metalloproteinases, tissue inhibitors of metalloproteinases, exosomes absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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“…Emerging evidence reinforces the concept that the tumour microenvironment is instrumental in tumourigenesis, particularly through the remodelling of the extracellular matrix (ECM). The degradation of the ECM by matrix metalloproteinases (MMPs) is a crucial action in tumour invasion that has a pivotal role in cancer dissemination [ 4 ]. However, the spread of cancer cells does not always lead to metastasis.…”

Section: Introductionmentioning

confidence: 99%

Stromal Cell-Derived Factor 1α (SDF-1α) in Invasive Breast Cancer: Associations with Vasculo-Angiogenic Factors and Prognostic Significance

Zarychta

Ruszkowska-Ciastek

Bielawski

et al. 2021

Cancers

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(1) Background: Tumour angiogenesis is critical for the progression of neoplasms. A prospective study was designed to examine the utility of stromal cell-derived factor 1α (SDF-1α) and selected vasculo-angiogenic parameters for estimating the probability of disease relapse in 84 primary, operable invasive breast cancer (IBrC) patients (40 (48%) with stage IA and 44 (52%) with stage IIA and IIB). (2) Methods: We explored the prognostic value of the plasma levels of SDF-1α, vascular endothelial growth factor A (VEGF-A), the soluble forms of VEGF receptors type 1 and 2, and the number of circulating endothelial progenitor cells (circulating EPCs) in breast cancer patients. The median follow-up duration was 58 months, with complete follow-up for the first event. (3) Results: According to ROC curve analysis, the optimal cut-off point for SDF-1α (for discriminating between patients at high and low risk of relapse) was 42 pg/mL, providing 57% sensitivity and 75% specificity. Kaplan–Meier curves for disease-free survival (DFS) showed that concentrations of SDF-1α lower than 42 pg/dL together with a VEGFR1 lower than 29.86 pg/mL were significantly associated with shorter DFS in IBrC patients (p = 0.0381). Patients with both SDF-1α lower than 42 pg/dL and a number of circulating EPCs lower than 9.68 cells/µL had significantly shorter DFS (p = 0.0138). (4) Conclusions: Our results imply the clinical usefulness of SDF-1α, sVEGFR1 and the number of circulating EPCs as prognostic markers for breast cancer in clinical settings.

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SDF-1 and MMP2 cross talk in cancer cells and tumor microenvironment in non-small cell lung cancer

Cited by 7 publications

References 56 publications

EpCAM-Targeted 3WJ RNA Nanoparticle Harboring Delta-5-Desaturase siRNA Inhibited Lung Tumor Formation via DGLA Peroxidation

EpCAM-Targeted 3WJ RNA Nanoparticle Harboring Delta-5-Desaturase siRNA Inhibited Lung Tumor Formation via DGLA Peroxidation

A Strong Decrease in TIMP3 Expression Mediated by the Presence of miR-17 and 20a Enables Extracellular Matrix Remodeling in the NSCLC Lesion Surroundings

Stromal Cell-Derived Factor 1α (SDF-1α) in Invasive Breast Cancer: Associations with Vasculo-Angiogenic Factors and Prognostic Significance

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