scholarly journals Octreotide-Targeted Lcn2 siRNA PEGylated Liposomes as a Treatment for Metastatic Breast Cancer

2021 ◽  
Vol 8 (4) ◽  
pp. 44
Author(s):  
Vrinda Gote ◽  
Dhananjay Pal
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cell Line ◽  
Cancer Progression ◽  
Somatostatin Receptors ◽  
Metastatic Breast ◽  
Mesenchymal Transition ◽  
Pegylated Liposomes ◽  
Mcf 7

Lcn2 overexpression in metastatic breast cancer (MBC) can lead to cancer progression by inducing the epithelial-to-mesenchymal transition and enhancing tumor angiogenesis. In this study, we engineered a PEGylated liposomal system encapsulating lipocalin 2 (Lcn2) small interfering RNA (Lcn2 siRNA) for selective targeting MBC cell line MCF-7 and triple-negative breast cancer cell line MDA-MB-231. The PEGylated liposomes were decorated with octreotide (OCT) peptide. OCT is an octapeptide analog of somatostatin growth hormone, having affinity for somatostatin receptors, overexpressed on breast cancer cells. Optimized OCT-targeted Lcn2 siRNA encapsulated PEGylated liposomes (OCT-Lcn2-Lipo) had a mean size of 152.00 nm, PDI, 0.13, zeta potential 4.10 mV and entrapment and loading efficiencies of 69.5% and 7.8%, respectively. In vitro uptake and intracellular distribution of OCT-Lcn2-Lipo in MCF-7 and MDA-MB-231 and MCF-12A cells demonstrated higher uptake for the OCT-targeted liposomes at 6 h by flow cytometry and confocal microscopy. OCT-Lcn2-lipo could achieve approximately 55−60% silencing of Lcn2 mRNA in MCF-7 and MDA-MB-231 cells. OCT-Lcn2-Lipo also demonstrated in vitro anti-angiogenic effects in MCF-7 and MDA-MB-231 cells by reducing VEGF-A and reducing the endothelial cells (HUVEC) migration levels. This approach may be useful in inhibiting angiogenesis in MBC.

Capture of EpCAM-negative and vimentin-positive circulating cancer cells (CCCs) from blood of metastatic breast cancer patients using ApoStream.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21029-e21029
Author(s):  
Christopher Neal ◽  
Sujita Sukumaran ◽  
Vishal Gupta ◽  
Insiya Jafferji ◽  
Dave Hasegawa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Laser Scanning ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Mesenchymal Transition ◽  
Circulating Cancer Cells

e21029 Background: Up-regulation of epithelial mesenchymal transition (EMT) and the reduction of epithelial marker expression is associated with invasion, cancer progression, resistance to conventional therapies and poor prognosis. ApoStream, a novel continuous flow dielectrophoresis field-flow fractionation (DEP-FFF) device, was used to enable antibody-independent capture of circulating cancer cells (CCCs,also referred to as circulating tumor cells, CTC) for subsequent phenotyping of EMT markers. Methods: A side-by-side comparison of CellSearch and ApoStream was performed on 10 metastatic breast cancer patients. A multiplexed immunofluorescent assay and laser scanning cytometry analyses were used to unambiguously identify CK+/CD45–/DAPI+ CCCs and quantify their EpCAM and vimentin expression. Results: ApoStream recovered CK+/CD45–/DAPI+ CCCs from each breast cancer patient sample tested (mean=255 CCCs per 7.5 ml blood, see Table). ApoStream consistently recovered significantly higher number of CCCs compared to CellSearch (p=0.024). ApoStream recovered both EpCAM+ and EpCAM– CCCs in 50% and 90% of patients, respectively. Vimentin+ CCCs were isolated from 90% of patients. Conclusions: ApoStream’s higher capture efficiency demonstrated the majority of CCCs from breast cancer patients were EpCAM negative and vimentin-positive. ApoStream technology can be used to monitor CCCs undergoing EMT. [Table: see text]

3,6-dichloro-1,2,4,5-Tetrazine Assayed at High Doses in the Metastatic Breast Cancer Cell Line MDA-MB-231 Reduces Cell Numbers and Induces Apoptosis

2020 ◽  
Vol 16 (4) ◽  
pp. 546-550 ◽  
Author(s):  
Mohamed Abdelkarim ◽  
Khaoula Ben Younes ◽  
Ines Limam ◽  
Refka Guermazi ◽  
Amel Ben Ammaar ElGaaied ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cell Line ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cell Line ◽  
Metastatic Breast ◽  
Cancer Cell Line ◽  
Metastatic Breast Cancer Cell

Background: The lack of treatment options for patients with chemotherapy-resistant cancers is pushing the field toward the development of new therapies. 1,2,4,5-tetrazine derivatives are a class of heterocyclic compounds that exhibit a broad spectrum of antitumor activities. Objective: The purpose of this study was to assess the biological activity of four s-tetrazine derivatives by substitution of two chloride atom of 3,6-dichloro-1,2,4,5-tetrazine with long hydrophobic side chains. Methods: We analyzed the anti-proliferative effects of four s-tetrazine derivatives with MTT assay and their pro-apoptotic effect with AV/ IP flow cytometry analysis and Hoechst 33342 staining. Results: We demonstrated that 3,6-dichloro-1,2,4,5-tetrazine (compound (1)) has a cytotoxic effect and induces apoptosis. Conclusion: 3,6-dichloro-1,2,4,5-tetrazine presents a new cytotoxic drug against metastatic breast cancer cell line MDA-MB-231 in vitro.

scholarly journals Pyruvate carboxylase supports the pulmonary tropism of metastatic breast cancer

2018 ◽  
Author(s):  
Aparna Shinde ◽  
Tomasz Wilmanski ◽  
Hao Chen ◽  
Dorothy Teegarden ◽  
Michael K. Wendt
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Metastatic Breast Cancer ◽  
Cancer Progression ◽  
Copy Number ◽  
Pyruvate Carboxylase ◽  
Patient Survival ◽  
Metastatic Breast

AbstractBackground: Overcoming systemic dormancy and initiating secondary tumor grow under unique microenvironmental conditions is a major rate-limiting step in metastatic progression. Disseminated tumor cells encounter major changes in nutrient supplies and oxidative stresses compared to the primary tumor and must demonstrate significant metabolic plasticity to adapt to specific metastatic sites. Recent studies suggest that differential utilization of pyruvate sits as a critical node in determining the organotropism of metastatic breast cancer. Pyruvate carboxylase (PC) is key enzyme that converts pyruvate into oxaloacetate for utilization in gluconeogenesis and replenishment of the TCA cycle.Methods: Patient survival was analyzed with respect to gene copy number alterations and differential mRNA expression levels of PC. Expression of PC was analyzed in the MCF-10A, D2-HAN and the 4T1 breast cancer progression series under in vitro and in vivo growth conditions. PC expression was depleted via shRNAs and the impact on in vitro cell growth, mammary fat pad tumor growth, and pulmonary and non-pulmonary metastasis was assessed by bioluminescent imaging. Changes in glycolytic capacity, oxygen consumption and response to oxidative stress were quantified upon PC depletion.Results: Genomic copy number increases in PC were observed in 16-30% of metastatic breast cancer patients. High expression of PC mRNA was associated with decreased patient survival in the MCTI and METABRIC patient datasets. Enhanced expression of PC was not recapitulated in breast cancer progression models when analyzed under glucose-rich in vitro culture conditions. In contrast, PC expression was dramatically enhanced upon glucose deprivation and in vivo in pulmonary metastases. Depletion of PC led to a dramatic decrease in 4T1 pulmonary metastasis but did not affect orthotopic primary tumor growth. Tail vein inoculations confirmed the role of PC in facilitating pulmonary, but not extra-pulmonary tumor initiation. PC-depleted cells demonstrated a decrease in glycolytic capacity and oxygen consumption rates and an enhanced sensitivity to oxidative stress.Conclusions: Our studies indicate that PC is specifically required for the growth of breast cancer that has disseminated to the lungs. Overall, these findings point to the potential of targeting PC for the treatment of pulmonary metastatic breast cancer.

scholarly journals Metastasis: A Bane of Breast Cancer Therapy

2020 ◽  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Tumour Size ◽  
Metastatic Breast ◽  
Metastatic Potential ◽  
Breast Cancer Metastasis ◽  
Mesenchymal Transition

The underlying mechanisms of metastasis in patients with breast cancer is still poorly understood. Approximately 6% of patients with breast cancer present with metastasis at the time of diagnosis. Metastatic breast cancer is difficult to treat and patients with breast cancer with distant metastasis have a significantly lower 5-year survival rate compared to patients with localised breast cancer (27% and 99%, respectively). During breast cancer progression, tumour cells first metastasise to nearby draining lymph nodes and then to distant organs, primarily bone, lungs, liver, and brain. In this brief review, the authors discuss breast cancer metastasis, the role of epithelial–mesenchymal transition and the contributions of the immune system to the metastatic process. The authors also briefly discuss whether there is any relationship between tumour size and metastatic potential, and recent advances in treatment for metastatic breast cancer. The studies highlighted suggest that immunotherapy may play a more significant role in future patient care for metastatic breast cancer.

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