scholarly journals MicroRNAs and Extracellular Vesicles as Distinctive Biomarkers of Precocious and Advanced Stages of Breast Cancer Brain Metastases Development

2021 ◽  
Vol 22 (10) ◽  
pp. 5214
Author(s):  
Inês Figueira ◽  
Joana Godinho-Pereira ◽  
Sofia Galego ◽  
Joana Maia ◽  
János Haskó ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Brain Metastases ◽  
Extracellular Vesicles ◽  
Triple Negative ◽  
Survival Rates ◽  
Brain Parenchyma ◽  
Advanced Stages ◽  
Breast Cancer Brain Metastases

Triple negative breast cancer presents higher mortality and poorer survival rates than other breast cancer (BC) types, due to the proneness to brain metastases formation, which are usually diagnosed at advanced stages. Therefore, the discovery of BC brain metastases (BCBM) biomarkers appears pivotal for a timely intervention. With this work, we aimed to disclose microRNAs (miRNAs) and extracellular vesicles (EVs) in the circulation as biomarkers of BCBM formation. Using a BCBM animal model, we analyzed EVs in plasma by nanoparticle tracking analysis and ascertained their blood-brain barrier (BBB) origin by flow cytometry. We further evaluated circulating miRNAs by RT-qPCR and their brain expression by in situ hybridization. In parallel, a cellular model of BCBM formation, combining triple negative BC cells and BBB endothelial cells, was used to differentiate the origin of biomarkers. Established metastases were associated with an increased content of circulating EVs, particularly of BBB origin. Interestingly, deregulated miRNAs in the circulation were observed prior to BCBM detection, and their brain origin was suggested by matching alterations in brain parenchyma. In vitro studies indicated that miR-194-5p and miR-205-5p are expressed and released by BC cells, endothelial cells and during their interaction. These results highlight miRNAs and EVs as biomarkers of BCBM in early and advanced stages, respectively.

scholarly journals Neurosurgical Treatment of Breast Cancer Metastases to the Neurocranium

2011 ◽  
Vol 2011 ◽  
pp. 1-6
Author(s):  
Andreas M. Stark
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Therapeutic Option ◽  
Contrast Material ◽  
Brain Parenchyma ◽  
Breast Cancer Metastases ◽  
Perilesional Edema ◽  
Cancer Metastases ◽  
Before And After ◽  
Breast Cancer Brain Metastases

Breast cancer metastases to the neurocranium might involve the bone, the dura, or the brain parenchyma. The latter location is the far most common. The annual incidence of brain metastases in patients with breast cancer is in the range of 4–11 per 100.000 persons per year. Symptoms and findings mainly result from the location of the lesion. The diagnostic method of choice is magnetic resonance imaging before and after administration of contrast material. Breast cancer brain metastases present as solid, cystic, or partially cystic lesions with marked contrast enhancement and perilesional edema. The therapeutic option of choice is microsurgical resection whenever possible. Adjuvant treatment includes radiotherapy, radiosurgery, and/or chemotherapy.

scholarly journals CSIG-29. THE DUAL PI3K/mTOR-PATHWAY INHIBITOR GDC-0084 ACHIEVES ANTITUMOR ACTIVITY IN BREAST CANCER BRAIN METASTASES IN VITRO AND IN VIVO

2018 ◽  
Vol 20 (suppl_6) ◽  
pp. vi49-vi49
Author(s):  
Franziska Ippen ◽  
Christopher Alvarez-Breckenridge ◽  
Benjamin Kuter ◽  
Alexandria Fink ◽  
Ivanna Bihun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Antitumor Activity ◽  
Brain Metastases ◽  
Mtor Pathway ◽  
Breast Cancer Brain Metastases

scholarly journals Synergistic Antitumorigenic Activity of Calcitriol with Curcumin or Resveratrol is Mediated by Angiogenesis Inhibition in Triple Negative Breast Cancer Xenografts

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1739 ◽  
Author(s):  
Janice García-Quiroz ◽  
Rocío García-Becerra ◽  
Clara Santos-Cuevas ◽  
Gerardo J. Ramírez-Nava ◽  
Gabriela Morales-Guadarrama ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Concomitant Administration ◽  
Mammary Tumor Cells ◽  
Tumor Onset ◽  
G1 Cells

Calcitriol is a multitarget anticancer hormone; however, its effects on angiogenesis remain contradictory. Herein, we tested whether the antiangiogenic phytochemicals curcumin or resveratrol improved calcitriol antitumorigenic effects in vivo. Triple-negative breast cancer tumoral cells (MBCDF-T) were xenografted in nude mice, maintaining treatments for 3 weeks. Tumor onset, volume and microvessel density were significantly reduced in mice coadministered with calcitriol and curcumin (Cal+Cur). Vessel count was also reduced in mice simultaneously treated with calcitriol and resveratrol (Cal+Rsv). Cal+Cur and Cal+Rsv treatments resulted in less tumor activated endothelium, as demonstrated by decreased tumor uptake of integrin-targeted biosensors in vivo. The renal gene expression of Cyp24a1 and Cyp27b1 suggested increased calcitriol bioactivity in the combined regimens. In vitro, the phytochemicals inhibited both MBCDF-T and endothelial cells proliferation, while potentiated calcitriol’s ability to reduce MBCDF-T cell-growth and endothelial cells migration. Resveratrol induced endothelial cell death, as deduced by increased sub-G1 cells accumulation, explaining the reduced tumor vessel number in resveratrol-treated mice, which further diminished when combined with calcitriol. In conclusion, the concomitant administration of calcitriol with curcumin or resveratrol synergistically promoted anticancer effects in vitro and in vivo in human mammary tumor cells. Whereas the results suggest different mechanisms of action of the phytochemicals when coadministered with calcitriol, the converging biological effect was inhibition of tumor neoangiogenesis.

KISS1 tumor suppressor restricts angiogenesis of breast cancer brain metastases and sensitizes them to oncolytic virotherapy in vitro

2018 ◽  
Vol 417 ◽  
pp. 75-88 ◽  
Author(s):  
Mikhail E. Platonov ◽  
Anton V. Borovjagin ◽  
Natalya Kaverina ◽  
Ting Xiao ◽  
Zaira Kadagidze ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Suppressor ◽  
Brain Metastases ◽  
Oncolytic Virotherapy ◽  
Breast Cancer Brain Metastases

scholarly journals BSCI-04. TARGETING TRIPLE-NEGATIVE BREAST CANCER BRAIN METASTASES WITH A RE-ENGINEERED LUPUS AUTOANTIBODY

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i1-i2
Author(s):  
Shenqi Zhang ◽  
Christopher May ◽  
Anupama Shirali ◽  
Valentina Dubljevic ◽  
James Campbell ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Metastatic Tumor ◽  
Nucleoside Transporter ◽  
Cell Nuclei ◽  
Filter Model ◽  
Breast Cancer Brain Metastases ◽  
The Brain

Abstract An unusual lupus anti-DNA autoantibody, 3E10, has potential to be used against triple-negative breast cancer (TNBC) brain metastases. 3E10 penetrates live cell nuclei, inhibits DNA repair, and is selectively toxic to cancer cells with the PTEN and/or DNA-damage response (DDR)-deficiencies that are associated with brain metastases in TNBC. The ENT2 nucleoside transporter that 3E10 uses to cross cell membranes is highly expressed in tumors and in brain endothelial cells (BECs) at the blood-brain barrier (BBB), and 3E10 has previously delivered cargo proteins to ischemic brain in a rat stroke model. We have re-engineered 3E10 into an optimized fragment, called Deoxymab-1 (PAT-DX1), that has increased effect on PTEN/DDR-deficient tumor cells. In the present study we tested the ability of PAT-DX1 to cross the BBB and improve outcomes in a mouse model of TNBC brain metastases. PAT-DX1 crossed from apical to basolateral chambers in an hCMEC/D3 Transwell filter model of the BBB, and penetrated the nuclei of and was toxic to the brain-seeking 231-BR subclone of MDA-MB-231 TNBC cells, which harbors a loss of PTEN compared to parental cells. Brain metastases were generated in nude mice by intracardiac injection of 1.75x105 231-BR cells engineered for expression of luciferase, as confirmed by IVIS one week after injection. Mice with brain metastases were treated by tail vein injection of control (PBS, n=7) or DX1 (20 mg/kg, n=7) 3x/week for 4 weeks. Mice were observed for behavior and weights, and brain radiance efficiency was monitored by weekly IVIS to track metastatic tumor growth. PAT-DX1 significantly suppressed growth of brain metastases based on absolute and relative radiance efficiencies in the brain, increased the median survival of the mice from 38 to 52 days (P< 0.02), and was well tolerated. These results provide proof of concept for use of a re-engineered autoantibody against brain metastases.

scholarly journals TMIC-10. THE ROLE OF THE BRAIN MICROENVIRONMENT IN THE MIGRATION OF BREAST CANCER CELLS IN BRAIN METASTASES

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi249-vi249
Author(s):  
Cymon Kersch ◽  
Leslie Muldoon ◽  
DreeAnna Morris ◽  
Edward Neuwelt
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Αvβ3 Integrin ◽  
Human Breast ◽  
And Migration ◽  
Breast Cancer Brain Metastases ◽  
The Brain

Abstract BACKGROUND Breast cancer brain metastases have poor prognosis and few treatment options. When breast cancer cells invade the brain they interact with the vasculature and resident brain cells including microglia and astrocytes. We hypothesize that brain cells produce factors that enhance the growth and invasion of breast cancer cells in the brain. METHODS Human breast cancer cell lines (MDA-MB231BR-HER2 and HCC1954) were inoculated intracranially in athymic rats as xenograft models of brain metastasis. Brains were analyzed for pro-tumorigenic factor expression in the tumor microenvironment using fluorescent immunohistochemistry. In vitro assays assessed factors involved in breast cancer cell proliferation, morphology, and migration. RESULTS The tumor xenografts showed infiltration intothe perivascular space. Galectin-3 (Gal3), heparin-binding epidermal growth factor (HB-EGF), and Neuregulin (NRG1), factors known to interact with receptors expressed by breast cancer cells, co-localized with reactive microglia (Gal3) and astrocytes (HB-EGF and NRG1) in and around xenografts. In vitro, these factors individually increased HCC1954 cell proliferation and/or migration. In transwell co-culture assays, BV2 microglial cells increased the migration of HCC1954 cells >25 fold, which was prevented by cilengitide, an inhibitor of αvβ3-integrin cell adhesion protein. ELISA analysis demonstrated that BV2 microglia secrete Gal3 in the presence of HCC1954 cells. Gal3 is known to bind and induce clustering of αvβ3-integrin which is expressed on metastatic breast cancer cells. Immunohistochemistry of clinical specimens revealed that Gal3 is expressed in/around human breast cancer brain metastases. CONCLUSIONS These data suggest that factors produced in the tumor microenvironment promote the growth and migration of breast cancer cells in the brain. Gal3, produced and secreted by activated microglia in vitro and expressed in and around brain metastases, increases the invasive capability of breast cancer cells. The interactions of neoplastic cells with the brain environment may provide a target to improve therapy of brain metastases.

scholarly journals Delivery of miR-424-5p via Extracellular Vesicles Promotes the Apoptosis of MDA-MB-231 TNBC Cells in the Tumor Microenvironment

2021 ◽  
Vol 22 (2) ◽  
pp. 844
Author(s):  
Yueyuan Zhou ◽  
Yusuke Yamamoto ◽  
Fumitaka Takeshita ◽  
Tomofumi Yamamoto ◽  
Zhongdang Xiao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Adipose Tissue ◽  
Extracellular Vesicles ◽  
Stromal Cells ◽  
Triple Negative ◽  
Intratumoral Administration ◽  
Immunosuppressive Microenvironment

Programmed cell death ligand-1 (PD-L1) overexpressed on cancer cells has emerged as a key inhibitor that maintains the immunosuppressive microenvironment through its interaction with the PD-1 receptor in cancer. Here, we demonstrated that miR-424-5p delivery via extracellular vesicles (EVs) derived from adipose tissue-mesenchymal stromal cells (AT-MSCs) partly promotes proinflammation and enhances antitumor cytotoxicity in vitro and in vivo. Triple negative breast cancer (TNBC) exhibits increased expression of PD-L1, and PD-L1 is positively correlated with the overall survival of patients with TNBC. PD-L1 shows relatively higher expression in MDA-MB-231 (MM231) cells and can be downregulated by miR-424-5p. Furthermore, miR-424-5p transported by EVs can increase the secretion of proinflammatory cytokines, decrease the secretion of anti-inflammatory cytokines and promote the apoptosis of tumor cells. The intratumoral administration of miR-424-5p-EVs significantly slowed tumor growth. In conclusion, these results demonstrate that EVs may serve as a delivery system for novel immunotherapies for TNBC through the miR-424-5p/PD-L1 pathway.

H-Ferritin nanoparticle-mediated delivery of antibodies across a BBB in vitro model for treatment of brain malignancies

2021 ◽  
Author(s):  
Maria Antonietta Rizzuto ◽  
Roberta Dal Magro ◽  
Linda Barbieri ◽  
Laura Pandolfi ◽  
Anna Sguazzini-Viscontini ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
In Vitro Model ◽  
Primary Glioblastoma ◽  
Her2 Breast Cancer ◽  
Vitro Model ◽  
Breast Cancer Brain Metastases ◽  
Barrier Model

H-ferritin nanoconjugates of CTX and TZ are developed as carriers across the BBB to allow immunotherapy of primary glioblastoma and HER2+ breast cancer brain metastases. The reliability of the strategy is demonstrated using a transwell barrier model.

Sign in / Sign up

Export Citation Format

Share Document