scholarly journals Application of Synthetic Polymeric Scaffolds in Breast Cancer 3D Tissue Cultures and Animal Tumor Models

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Girdhari Rijal ◽  
Chandra Bathula ◽  
Weimin Li
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Three Dimensional ◽  
Tumor Formation ◽  
Porous Scaffolds ◽  
Tissue Cultures ◽  
Polymeric Scaffolds

Preparation of three-dimensional (3D) porous scaffolds from synthetic polymers is a challenge to most laboratories conducting biomedical research. Here, we present a handy and cost-effective method to fabricate polymeric hydrogel and porous scaffolds using poly(lactic-co-glycolic) acid (PLGA) or polycaprolactone (PCL). Breast cancer cells grown on 3D polymeric scaffolds exhibited distinct survival, morphology, and proliferation compared to those on 2D polymeric surfaces. Mammary epithelial cells cultured on PLGA- or PCL-coated slides expressed extracellular matrix (ECM) proteins and their receptors. Estrogen receptor- (ER-) positive T47D breast cancer cells are less sensitive to 4-hydroxytamoxifen (4-HT) treatment when cultured on the 3D porous scaffolds than in 2D cultures. Finally, cancer cell-laden polymeric scaffolds support consistent tumor formation in animals and biomarker expression as seen in human native tumors. Our data suggest that the porous synthetic polymer scaffolds satisfy the basic requirements for 3D tissue cultures both in vitro and in vivo. The scaffolding technology has appealing potentials to be applied in anticancer drug screening for a better control of the progression of human cancers.

Abstract 246: Translocation Of Myomirs Via Gap Junction Channels Prevents Cancer Cell Growth

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Laura Graciotti ◽  
Toru Hosoda ◽  
Marcello Rota ◽  
Giulia Borghetti ◽  
Sergio Signore ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gap Junctions ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Connexin 43 ◽  
Breast Cancer Cells ◽  
Fold Increase ◽  
Tumor Formation

The adult heart is resistant to cancer formation and the metastatic invasion of distant neoplasms. This biological advantage may be dictated by the molecular properties of myocytes that constitutes 90% of the myocardium. We raised the possibility that microRNAs (miRs) highly expressed in myocytes (myomirs) may translocate via gap junctions to neighboring cancer cells, preventing their growth or inhibiting their survival. First, we established whether overexpression of myomirs interferes with the proliferation and death of MCF7 human breast cancer cells. Infection of MCF7 with lentiviruses carrying miR-1, miR-133a and miR-499 (miR-MCF7) resulted in a 5-fold decrease in Ki67 labeling and a 20% increase in the fraction of cells arrested at G0/G1. In contrast, TdT-positive apoptotic cells averaged 0.5% and did not differ in miR-MCF7 and control cells. To mimic the in vivo condition, EGFP-labeled MCF7 were co-cultured with myocytes and, 4 days later, the expression of myomirs was measured in FACS-sorted MCF7. With respect to baseline, co-cultured MCF7 showed 100-fold, 16-fold, and 27-fold increase in the expression of miR-1, miR-133a and miR-499, respectively. Co-culture of myocytes and MCF7 led to the formation of gap junctions made of connexin 43 (Cx43) and connexin 45 (Cx45). Silencing of Cx43 and Cx45 decreased significantly the expression of myomirs in co-cultured MCF7. Importantly, proximity of MCF7 to myocytes reduced markedly the growth rate of the cancer cells. Subsequently, 1 x 106 MCF7 or miR-MCF7 were injected subcutaneously in NOD-scid mice. At 5 weeks, the tumors developed from miR-MCF7 were 70% smaller than those originated from control MCF7. Two doses of breast cancer cells were injected intramyocardially to establish their in situ tumorigenic effects. Tumor formation was found in all hearts that received 1 x 106 MCF7. Conversely, mice injected with 1 x 105 cells did not show macroscopic evidence of neoplastic lesions. The lack of tumor development in the latter case is consistent with the ability of the heart to prevent neoplasm development when cancer cell colonization is not massive. Our findings document that miR-1, miR-133a and miR-499 translocate from myocytes to cancer cells via gap junctions, inhibiting tumor growth in vitro and in vivo.

scholarly journals Parvin-β Inhibits Breast Cancer Tumorigenicity and Promotes CDK9-Mediated Peroxisome Proliferator-Activated Receptor Gamma 1 Phosphorylation

2007 ◽  
Vol 28 (2) ◽  
pp. 687-704 ◽  
Author(s):  
Cameron N. Johnstone ◽  
Perry S. Mongroo ◽  
A. Sophie Rich ◽  
Michael Schupp ◽  
Mark J. Bowser ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Three Dimensional ◽  
Nuclear Hormone Receptor ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

ABSTRACT Parvin-β is a focal adhesion protein downregulated in human breast cancer cells. Loss of Parvin-β contributes to increased integrin-linked kinase activity, cell-matrix adhesion, and invasion through the extracellular matrix in vitro. The effect of ectopic Parvin-β expression on the transcriptional profile of MDA-MB-231 breast cancer cells, which normally do not express Parvin-β, was evaluated. Particular emphasis was placed upon propagating MDA-MB-231 breast cancer cells in three-dimensional culture matrices. Interestingly, Parvin-β reexpression in MDA-MB-231 cells increased the mRNA expression, serine 82 phosphorylation (mediated by CDK9), and activity of the nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARγ), and there was a concomitant increase in lipogenic gene expression as a downstream effector of PPARγ. Importantly, Parvin-β suppressed breast cancer growth in vivo, with associated decreased proliferation. These data suggest that Parvin-β might influence breast cancer progression.

scholarly journals In Vivo Cell Fusion between Mesenchymal Stroma/Stem-Like Cells and Breast Cancer Cells

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 185 ◽  
Author(s):  
Catharina Melzer ◽  
Juliane von der Ohe ◽  
Ralf Hass
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Fusion ◽  
Breast Cancer Cells ◽  
Rare Event ◽  
Tumor Formation ◽  
Hybrid Cells ◽  
Mesenchymal Stroma

Cellular communication within the tumor microenvironment enables important interactions between cancer cells and recruited adjacent populations including mesenchymal stroma/stem-like cells (MSC). These interactions were monitored in vivo following co-injection of GFP-labeled human MSC together with mcherry-labeled MDA-MB-231 breast cancer cells in NODscid mice. Within 14 days of tumor development the number of initially co-injected MSC had significantly declined and spontaneous formation of breast cancer/MSC hybrid cells was observed by the appearance of double fluorescing cells. This in vivo fusion displayed a rare event and occurred in less than 0.5% of the tumor cell population. Similar findings were observed in a parallel in vitro co-culture. Characterization of the new cell fusion products obtained after two consecutive flow cytometry cell sorting and single cell cloning revealed two populations, termed MDA-hyb3 and MDA-hyb4. The breast cancer fusion cells expressed both, GFP and mcherry and displayed more characteristics of the MDA-MB-231 cells than of the parental MSC. While little if any differences were determined in the proliferative capacity, a significant delay of MDA-hyb3 cells in tumor formation was observed when compared to the parental MDA-MB-231 cells. Moreover, MDA-hyb3 cells developed an altered pattern of distant organ metastases. These findings demonstrated dynamic tumor changes by in vivo and in vitro fusion with the development of new breast cancer hybrid cells carrying altered tumorigenic properties. Consequently, cancer cell fusion contributes to progressively increasing tumor heterogeneity which complicates a therapeutic regimen.

scholarly journals A Benzochalcone Derivative, (E)-1-(2-hydroxy-6-methoxyphenyl)-3-(naphthalen-2-yl)prop-2-en-1-one (DK-512), Inhibits Tumor Invasion through Inhibition of the TNFα-Induced NF-κB/MMP-9 Axis in MDA-MB-231 Breast Cancer Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-8
Author(s):  
Soon Young Shin ◽  
Chang Gun Kim ◽  
Seunghyun Ahn ◽  
You Jung Jung ◽  
Dongsoo Koh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Extracellular Matrix ◽  
Cancer Cells ◽  
Tumor Invasion ◽  
Breast Cancer Cells ◽  
Three Dimensional ◽  
Extracellular Matrix Components ◽  
System Tumor

Tumor invasion is a critical step in tumor metastasis. In this study, we synthesized a novel benzochalcone derivative, (E)-1-(2-hydroxy-6-methoxyphenyl)-3-(naphthalen-2-yl) prop-2-en-1-one (DK-512), and characterized its effects on tumor invasion and its mechanism of action. We found that DK-512 strongly inhibited invasion of metastatic MDA-MB-231 breast cancer cells as revealed by a three-dimensional spheroid culture system. Tumor invasion and metastasis require disruption of the extracellular matrix. Matrix metalloproteinase-9 (MMP-9) is an endopeptidase that degrades extracellular matrix components. DK-512 significantly reduced tumor necrosis factor-α- (TNFα-) induced MMP-9 mRNA expression through the inhibition of RelA nuclear factor- (NF-)κB transcription factor. As our study was assessedin vitro, further works aboutin vivoefficacy of DK-512 are needed to gain further insights into whether DK-512 could be utilized as a scaffold for the development of antimetastatic agents for breast cancer.

Targeting PKM2 promotes chemosensitivity of breast cancer cells in vitro and in vivo

2021 ◽  
pp. 1-10
Author(s):  
Yu Wang ◽  
Han Zhao ◽  
Ping Zhao ◽  
Xingang Wang
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Poor Prognosis ◽  
Breast Cancer Cells ◽  
Breast Cancer Patients ◽  
Cancer Tissues

BACKGROUND: Pyruvate kinase M2 (PKM2) was overexpressed in many cancers, and high PKM2 expression was related with poor prognosis and chemoresistance. OBJECTIVE: We investigated the expression of PKM2 in breast cancer and analyzed the relation of PKM2 expression with chemotherapy resistance to the neoadjuvant chemotherapy (NAC). We also investigated whether PKM2 could reverse chemoresistance in breast cancer cells in vitro and in vivo. METHODS: Immunohistochemistry (IHC) was performed in 130 surgical resected breast cancer tissues. 78 core needle biopsies were collected from breast cancer patients before neoadjuvant chemotherapy. The relation of PKM2 expression and multi-drug resistance to NAC was compared. The effect of PKM2 silencing or overexpression on Doxorubicin (DOX) sensitivity in the MCF-7 cells in vitro and in vivo was compared. RESULTS: PKM2 was intensively expressed in breast cancer tissues compared to adjacent normal tissues. In addition, high expression of PKM2 was associated with poor prognosis in breast cancer patients. The NAC patients with high PKM2 expression had short survival. PKM2 was an independent prognostic predictor for surgical resected breast cancer and NAC patients. High PKM2 expression was correlated with neoadjuvant treatment resistance. High PKM2 expression significantly distinguished chemoresistant patients from chemosensitive patients. In vitro and in vivo knockdown of PKM2 expression decreases the resistance to DOX in breast cancer cells in vitro and tumors in vivo. CONCLUSION: PKM2 expression was associated with chemoresistance of breast cancers, and could be used to predict the chemosensitivity. Furthermore, targeting PKM2 could reverse chemoresistance, which provides an effective treatment methods for patients with breast cancer.

scholarly journals Controllable Drug Delivery by Na+/K+ ATPase α1 Targeting Peptide Conjugated DSPE-PEG Nanocarriers for Breast Cancer

2021 ◽  
Vol 20 ◽  
pp. 153303382110278
Author(s):  
Yayan Yang ◽  
Qian Feng ◽  
Chuanfeng Ding ◽  
Wei Kang ◽  
Xiufeng Xiao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Click Reaction ◽  
Chemotherapy Drugs ◽  
Targeting Peptide ◽  
And Migration

Although Epirubicin (EPI) is a commonly used anthracycline for the treatment of breast cancer in clinic, the serious side effects limit its long-term administration including myelosuppression and cardiomyopathy. Nanomedicines have been widely utilized as drug delivery vehicles to achieve precise targeting of breast cancer cells. Herein, we prepared a DSPE-PEG nanocarrier conjugated a peptide, which targeted the breast cancer overexpression protein Na+/K+ ATPase α1 (NKA-α1). The nanocarrier encapsulated the EPI and grafted with the NKA-α1 targeting peptide through the click reaction between maleimide and thiol groups. The EPI was slowly released from the nanocarrier after entering the breast cancer cells with the guidance of the targeting NKA-α1 peptide. The precise and controllable delivery and release of the EPI into the breast cancer cells dramatically inhibited the cells proliferation and migration in vitro and suppressed the tumor volume in vivo. These results demonstrate significant prospects for this nanocarrier as a promising platform for numerous chemotherapy drugs.

scholarly journals Integrin α3β1 Promotes Invasive and Metastatic Properties of Breast Cancer Cells through Induction of the Brn-2 Transcription Factor

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 480
Author(s):  
Rakshitha Pandulal Miskin ◽  
Janine S. A. Warren ◽  
Abibatou Ndoye ◽  
Lei Wu ◽  
John M. Lamar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Cancer Cells ◽  
Cell Invasion ◽  
Breast Cancer Cells ◽  
Gene Promoter ◽  
Akt Inhibitor ◽  
Integrin Α3β1

In the current study, we demonstrate that integrin α3β1 promotes invasive and metastatic traits of triple-negative breast cancer (TNBC) cells through induction of the transcription factor, Brain-2 (Brn-2). We show that RNAi-mediated suppression of α3β1 in MDA-MB-231 cells caused reduced expression of Brn-2 mRNA and protein and reduced activity of the BRN2 gene promoter. In addition, RNAi-targeting of Brn-2 in MDA-MB-231 cells decreased invasion in vitro and lung colonization in vivo, and exogenous Brn-2 expression partially restored invasion to cells in which α3β1 was suppressed. α3β1 promoted phosphorylation of Akt in MDA-MB-231 cells, and treatment of these cells with a pharmacological Akt inhibitor (MK-2206) reduced both Brn-2 expression and cell invasion, indicating that α3β1-Akt signaling contributes to Brn-2 induction. Analysis of RNAseq data from patients with invasive breast carcinoma revealed that high BRN2 expression correlates with poor survival. Moreover, high BRN2 expression positively correlates with high ITGA3 expression in basal-like breast cancer, which is consistent with our experimental findings that α3β1 induces Brn-2 in TNBC cells. Together, our study demonstrates a pro-invasive/pro-metastatic role for Brn-2 in breast cancer cells and identifies a role for integrin α3β1 in regulating Brn-2 expression, thereby revealing a novel mechanism of integrin-dependent breast cancer cell invasion.

In vitro evaluation of estrogenic, antiestrogenic and antitumor effects of amentoflavone

2021 ◽  
pp. 096032712199945
Author(s):  
AT Aliyev ◽  
S Ozcan-Sezer ◽  
A Akdemir ◽  
H Gurer-Orhan
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Antitumor Effects ◽  
Antiestrogenic Activity ◽  
Er Positive ◽  
In Vivo Effects ◽  
Mcf 7

Apigenin, a flavonoid, is reported to act as an estrogen receptor (ER) agonist and inhibit aromatase enzyme. However, amentoflavone, a biflavonoid bearing two apigenin molecules, has not been evaluated for its endocrine modulatory effects. Besides, it is highly consumed by young people to build muscles, enhance mood and lose weight. In the present study, apigenin was used as a reference molecule and ER mediated as well as ER-independent estrogenic/antiestrogenic activity of amentoflavone was investigated. Antitumor activity of amentoflavone was also investigated in both ER positive (MCF-7 BUS) and triple-negative (MDA-MB-231) breast cancer cells and its cytotoxicity was evaluated in human breast epithelial cells (MCF-10A). Our data confirmed ER agonist, aromatase inhibitory and cytotoxic effects of apigenin in breast cancer cells, where no ER mediated estrogenic effect and physiologically irrelevant, slight, aromatase inhibition was found for amentoflavone. Although selective cytotoxicity of amentoflavone was found in MCF-7 BUS cells, it does not seem to be an alternative to the present cytotoxic drugs. Therefore, neither an adverse effect, mediated by an estrogenic/antiestrogenic effect of amentoflavone nor a therapeutical benefit would be expected from amentoflavone. Further studies could be performed to investigate its in vivo effects.

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