scholarly journals CBIO-02. COMPREHENSIVE ANALYSIS OF MECHANISMS AND MOLECULAR TARGETS FOR BREAST CANCER LEPTOMENINGEAL METASTASIS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii16-ii16
Author(s):  
Noriyuki Kijima ◽  
Takamune Achiha ◽  
Tomoyoshi Nakagawa ◽  
Ryuichi Hirayama ◽  
Manabu Kinoshita ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Spinal Cord ◽  
Extracellular Matrix ◽  
Cerebrospinal Fluid ◽  
Tumor Cells ◽  
Fluorescent Protein ◽  
Cancer Cell Line ◽  
Leptomeningeal Metastasis ◽  
Solid Cancer ◽  
Related Proteins

Abstract Leptomeningeal metastasis from solid cancer is a devastating state for cancer patients. Leptomeningeal metastasis is diagnosed either by cerebrospinal fluid cytology and/or magnetic resonance imaging (MRI). However, it remains unclear as to whether tumor cells attached to leptomeninges are the same from floating tumor cells in cerebrospinal fluid (CSF). In this study, we aim to analyze the differences between tumor cells attached to leptomeninges and floating cells in CSF by xenograft models. We used breast cancer cell line, MDA-MB-231, labelled with green fluorescent protein (GFP) and luciferase. We injected those cells into right lateral ventricle of NOD/Shi-scid IL2Rγ KO mice. When the mice got any signs of tumor, we dissected spinal cord and got CSF from mice. We sorted tumor cells by flow cytometry and extracted RNA from the sorted tumor cells from spinal cord and CSF, respectively. We analyzed transcriptome differences between tumor cells from spinal cord and CSF by RNA sequencing. We found that extracellular matrix related proteins were highly upregulated while cell growth related proteins were downregulated in tumor cells from spinal cord compared with those from CSF. These results suggest that tumor cells attached to leptomeninges have different transcriptome profiles from floating tumor cells in CSF and extracellular matrix related proteins could be therapeutic targets for breast cancer leptomeningeal metastasis.

Detection of cerebrospinal fluid tumor cells and its clinical relevance in leptomeningeal metastasis of breast cancer

2015 ◽  
Vol 154 (2) ◽  
pp. 339-349 ◽  
Author(s):  
Jin Sun Lee ◽  
Michelle E. Melisko ◽  
Mark Jesus M. Magbanua ◽  
Andrea T. Kablanian ◽  
Janet H. Scott ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cerebrospinal Fluid ◽  
Tumor Cells ◽  
Clinical Relevance ◽  
Leptomeningeal Metastasis

scholarly journals Identification of leptomeningeal metastasis-related proteins in cerebrospinal fluid of patients with breast cancer by a combination of MALDI-TOF, MALDI-FTICR and nanoLC-FTICR MS

PROTEOMICS ◽  
2007 ◽  
Vol 7 (3) ◽  
pp. 474-481 ◽  
Author(s):  
Andreas Römpp ◽  
Lennard Dekker ◽  
Ioana Taban ◽  
Guido Jenster ◽  
Willem Boogerd ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cerebrospinal Fluid ◽  
Leptomeningeal Metastasis ◽  
Fticr Ms ◽  
Maldi Tof ◽  
Related Proteins

scholarly journals Oriented collagen fibers direct tumor cell intravasation

2016 ◽  
Vol 113 (40) ◽  
pp. 11208-11213 ◽  
Author(s):  
Weijing Han ◽  
Shaohua Chen ◽  
Wei Yuan ◽  
Qihui Fan ◽  
Jianxiang Tian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Extracellular Matrix ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Fiber Orientation ◽  
Breast Cancer Cells ◽  
Protein Concentration ◽  
Collagen Fiber ◽  
Fiber Alignment ◽  
Local Fiber

In this work, we constructed a Collagen I–Matrigel composite extracellular matrix (ECM). The composite ECM was used to determine the influence of the local collagen fiber orientation on the collective intravasation ability of tumor cells. We found that the local fiber alignment enhanced cell–ECM interactions. Specifically, metastatic MDA-MB-231 breast cancer cells followed the local fiber alignment direction during the intravasation into rigid Matrigel (∼10 mg/mL protein concentration).

scholarly journals Breast Tumor Cells Highly Resistant to Drugs Are Controlled Only by the Immune Response Induced in an Immunocompetent Mouse Model

2019 ◽  
Vol 18 ◽  
pp. 153473541984804 ◽  
Author(s):  
Paola Lasso ◽  
Mónica Llano Murcia ◽  
Tito Alejandro Sandoval ◽  
Claudia Urueña ◽  
Alfonso Barreto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Tumor Cells ◽  
High Capacity ◽  
Cancer Cell Line ◽  
Tumor Model ◽  
Main Element ◽  
In Vivo Models

Background: The tumor cells responsible for metastasis are highly resistant to chemotherapy and have characteristics of stem cells, with a high capacity for self-regeneration and the use of detoxifying mechanisms that participate in drug resistance. In vivo models of highly resistant cells allow us to evaluate the real impact of the immune response in the control of cancer. Materials and Methods: A tumor population derived from the 4T1 breast cancer cell line that was stable in vitro and highly aggressive in vivo was obtained, characterized, and determined to exhibit cancer stem cell (CSC) phenotypes (CD44+, CD24+, ALDH+, Oct4+, Nanog+, Sox2+, and high self-renewal capacity). Orthotopic transplantation of these cells allowed us to evaluate their in vivo susceptibility to chemo and immune responses induced after vaccination. Results: The immune response induced after vaccination with tumor cells treated with doxorubicin decreased the formation of tumors and macrometastasis in this model, which allowed us to confirm the immune response relevance in the control of highly chemotherapy-resistant ALDH+ CSCs in an aggressive tumor model in immunocompetent animals. Conclusions: The antitumor immune response was the main element capable of controlling tumor progression as well as metastasis in a highly chemotherapy-resistant aggressive breast cancer model.

Silibinin Inhibit Cell Migration through Downregulation of RAC1 Gene Expression in Highly Metastatic Breast Cancer Cell Line

Drug Research ◽  
2020 ◽  
Vol 70 (10) ◽  
pp. 478-483
Author(s):  
Hamed Esmaeil Lashgarian ◽  
Vahid Adamii ◽  
Vajihe Ghorbanzadeh ◽  
Leila Chodari ◽  
Fayze Kamali ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Tumor Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cell Line ◽  
Cancer Cell Line ◽  
Migration And Invasion ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background Triple negative breast cancer is the most invasive breast cancer subtype and possesses poor prognosis and survival. Rho GTPase famil, especially Rac1 participates in a number of signaling events in cells with crucial roles in malignancy, migration and invasion of tumor cells. Silibinin, a flavonoid antioxidant from milk thistle has attracted attention in the recent decades for chemoprevention and chemotherapy of tumor cells. In this study, the effect of silibinin on the migration capacity of MDA-MB-231 cells, a highly metastatic human breast cancer cell line was investigated by evaluation of Rac1 expression. Method MTT wound healing and transwell assays were performed to evaluate the effects of silibinin on proliferation and migration of MDA-MB-231 cells. In addition, the influence of the silibinin on the expression of Rac1mRNAs was assessed by RT-PCR. Results Results indicated significant dose-dependent inhibitory effect of silibinin on proliferation and migration of MDA-MB-231 cells. It significantly inhibited the expression of Rac1 mRNA. Conclusion In conclusion, the results demonstrate that the silibinin can be used as an experimental therapeutic for the management of TNBC metastatic cancer.

scholarly journals N-WASP coordinates the delivery and F-actin–mediated capture of MT1-MMP at invasive pseudopods

2012 ◽  
Vol 199 (3) ◽  
pp. 527-544 ◽  
Author(s):  
Xinzi Yu ◽  
Tobias Zech ◽  
Laura McDonald ◽  
Esther Garcia Gonzalez ◽  
Ang Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Extracellular Matrix ◽  
Plasma Membrane ◽  
Tumor Cells ◽  
Matrix Metalloproteases ◽  
Matrix Remodeling ◽  
Dense Matrix ◽  
Matrix Degradation ◽  
Late Endosomes ◽  
Syndrome Protein

Metastasizing tumor cells use matrix metalloproteases, such as the transmembrane collagenase MT1-MMP, together with actin-based protrusions, to break through extracellular matrix barriers and migrate in dense matrix. Here we show that the actin nucleation–promoting protein N-WASP (Neural Wiskott-Aldrich syndrome protein) is up-regulated in breast cancer, and has a pivotal role in mediating the assembly of elongated pseudopodia that are instrumental in matrix degradation. Although a role for N-WASP in invadopodia was known, we now show how N-WASP regulates invasive protrusion in 3D matrices. In actively invading cells, N-WASP promoted trafficking of MT1-MMP into invasive pseudopodia, primarily from late endosomes, from which it was delivered to the plasma membrane. Upon MT1-MMP’s arrival at the plasma membrane in pseudopodia, N-WASP stabilized MT1-MMP via direct tethering of its cytoplasmic tail to F-actin. Thus, N-WASP is crucial for extension of invasive pseudopods into which MT1-MMP traffics and for providing the correct cytoskeletal framework to couple matrix remodeling with protrusive invasion.

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