scholarly journals miR-205-5p Downregulation and ZEB1 Upregulation Characterize the Disseminated Tumor Cells in Patients with Invasive Ductal Breast Cancer

2021 ◽  
Vol 23 (1) ◽  
pp. 103
Author(s):  
Lenka Kalinkova ◽  
Nataliia Nikolaieva ◽  
Bozena Smolkova ◽  
Sona Ciernikova ◽  
Karol Kajo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epithelial To Mesenchymal Transition ◽  
Disseminated Tumor Cells ◽  
Metastatic Potential ◽  
Rt Pcr ◽  
Invasive Front ◽  
Mesenchymal Transition ◽  
Prognostic Features ◽  
Invasive Ductal Breast Cancer ◽  
Ductal Breast Cancer

Background: Dissemination of breast cancer (BC) cells through the hematogenous or lymphogenous vessels leads to metastatic disease in one-third of BC patients. Therefore, we investigated the new prognostic features for invasion and metastasis. Methods: We evaluated the expression of miRNAs and epithelial-to-mesenchymal transition (EMT) genes in relation to CDH1/E-cadherin changes in samples from 31 patients with invasive ductal BC including tumor centrum (TU-C), tumor invasive front (TU-IF), lymph node metastasis (LNM), and CD45-depleted blood (CD45-DB). Expression of miRNA and mRNA was quantified by RT-PCR arrays and associations with clinico-pathological characteristics were statistically evaluated by univariate and multivariate analysis. Results: We did not verify CDH1 regulating associations previously described in cell lines. However, we did detect extremely high ZEB1 expression in LNMs from patients with distant metastasis, but without regulation by miR-205-5p. Considering the ZEB1 functions, this overexpression indicates enhancement of metastatic potential of lymphogenously disseminated BC cells. In CD45-DB samples, downregulated miR-205-5p was found in those expressing epithelial and/or mesenchymal markers (CTC+) that could contribute to insusceptibility and survival of hematogenously disseminated BC cells mediated by increased expression of several targets including ZEB1. Conclusions: miR-205-5p and potentially ZEB1 gene are promising candidates for markers of metastatic potential in ductal BC.

Two possible mechanisms of epithelial to mesenchymal transition in invasive ductal breast cancer

2011 ◽  
Vol 28 (8) ◽  
pp. 811-818 ◽  
Author(s):  
Sylvie Dubois-Marshall ◽  
Jeremy S. Thomas ◽  
Dana Faratian ◽  
David J. Harrison ◽  
Elad Katz
Keyword(s):  
Breast Cancer ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Invasive Ductal Breast Cancer ◽  
Ductal Breast Cancer

scholarly journals Pivotal Role of AKT2 during Dynamic Phenotypic Change of Breast Cancer Stem Cells

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1058 ◽  
Author(s):  
Gener ◽  
Rafael ◽  
Seras-Franzoso ◽  
Perez ◽  
Pindado ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Distant Metastases ◽  
Metastatic Potential ◽  
Phenotypic Change ◽  
Primary Tumors ◽  
Mesenchymal Transition

Therapeutic resistance seen in aggressive forms of breast cancer remains challenging for current treatments. More than half of the patients suffer from a disease relapse, most of them with distant metastases. Cancer maintenance, resistance to therapy, and metastatic disease seem to be sustained by the presence of cancer stem cells (CSC) within a tumor. The difficulty in targeting this subpopulation derives from their dynamic interconversion process, where CSC can differentiate to non-CSC, which in turn de-differentiate into cells with CSC properties. Using fluorescent CSC models driven by the expression of ALDH1A 1(aldehyde dehydrogenase 1A1), we confirmed this dynamic phenotypic change in MDA-MB-231 breast cancer cells and to identify Serine/Threonine Kinase 2 (AKT2) as an important player in the process. To confirm the central role of AKT2, we silenced AKT2 expression via small interfering RNA and using a chemical inhibitor (CCT128930), in both CSC and non-CSC from different cancer cell lines. Our results revealed that AKT2 inhibition effectively prevents non-CSC reversion through mesenchymal to epithelial transition, reducing invasion and colony formation ability of both, non-CSC and CSC. Further, AKT2 inhibition reduced CSC survival in low attachment conditions. Interestingly, in orthotopic tumor mouse models, high expression levels of AKT2 were detected in circulating tumor cells (CTC). These findings suggest AKT2 as a promising target for future anti-cancer therapies at three important levels: (i) Epithelial-to-mesenchymal transition (EMT) reversion and maintenance of CSC subpopulation in primary tumors, (ii) reduction of CTC and the likelihood of metastatic spread, and (iii) prevention of tumor recurrence through inhibition of CSC tumorigenic and metastatic potential.

scholarly journals Morphological features of invasion of tumor cells of invasive ductal breast cancer

Morphologia ◽  
2021 ◽  
Vol 15 (3) ◽  
pp. 119-124
Author(s):  
L.A. Naleskina ◽  
T.V. Zadvornyi ◽  
L.M. Kunska ◽  
N.Y. Lukianova
Keyword(s):  
Breast Cancer ◽  
Connective Tissue ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Invasion ◽  
Tumor Cell Invasion ◽  
Invasive Front ◽  
Invasive Ductal Breast Cancer ◽  
Pathological Characteristics ◽  
Ductal Breast Cancer

Background. Nowadays, it has been proven that along with the invasion of individual tumor cells, their group migration occurs in the invasive front of the tumor, and this is an important factor in tumor progression. Objective: to determine the features of tumor cell invasion in the invasive front (IF) of invasive ductal breast cancer (BCa) without special specific features (IC NST) and to establish associative links between them and the clinical and pathological characteristics of the disease. Methods. The study was performed on BCa samples (after hematoxylin and eosin stained) from 120 patients with invasive ductal BCa I-II stage with G2 grade of tumor differentiation that didn’t receive neoadjuvant chemotherapy. Results. Tumors were divided into 3 groups: with predominance of parenchymal component (PC), with the larger component of connective tissue, and relatively equivalent ratio of these components. Within the IF of the studied tumors of patients with ІІ stage of the tumor process, group invasion of tumor structures was mainly determined, both separately and in combination. In particular, an increase in solid structures in tumors with a predominance of the PC, and in neoplasms with expressed desmoplastic changes in connective tissue and their advantage, - alveolar, tubular, discrete. Conclusion. In tumors of patients with invasive ductal BCa in the invasive front is dominated by collective migration of tumor cells, which is the starting mechanism of tumor progression and the first step of the metastatic process. Defined associative links between the features of tumor cell invasion and the clinical and pathological characteristics of the tumor process in BCa patients can be used in predicting this form of cancer.

E2F3 drives the epithelial-to-mesenchymal transition, cell invasion, and metastasis in breast cancer

2021 ◽  
pp. 153537022110356
Author(s):  
Shirley Jusino ◽  
Yainyrette Rivera-Rivera ◽  
Camille Chardón-Colón ◽  
Armando J Ruiz-Justiz ◽  
Jaleisha Vélez-Velázquez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Invasion ◽  
Epithelial To Mesenchymal Transition ◽  
Chromosome Instability ◽  
Metastatic Potential ◽  
Metastatic Progression ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
Tumor Growth And Metastasis ◽  
And Migration

E2F3 is a transcription factor that may initiate tumorigenesis if overexpressed. Previously, we demonstrated that E2F3 mRNA is overexpressed in breast cancer and that E2F3 overexpression results in centrosome amplification and unregulated mitosis, which can promote aneuploidy and chromosome instability to initiate and sustain tumors. Further, we demonstrated that E2F3 leads to overexpression of the mitotic regulator Shugoshin-1, which until recently had unknown roles in cancer. This study aims to evaluate the roles of E2F3 and Shugoshin-1 in breast cancer metastatic potential. Here we demonstrated that E2F3 and Shugoshin-1 silencing leads to reduced cell invasion and migration in two mesenchymal triple-negative breast cancer (TNBC) cell lines (MDA-MB-231 and Hs578t). Moreover, E2F3 and Shugoshin-1 modulate the expression of epithelial-to-mesenchymal transition-associated genes such as Snail, E-Cadherin, and multiple matrix metalloproteinases. Furthermore, E2F3 depletion leads to reductions in tumor growth and metastasis in NOD- scid Gamma mice. Results from this study suggest a key role for E2F3 and a novel role for Shugoshin-1 in metastatic progression. These results can further help in the improvement of TNBC targeted therapies by interfering with pathways that intersect with the E2F3 and Shugoshin-1 signaling pathways.

scholarly journals Dissection of major cancer gene variants in subsets of circulating tumor cells in advanced breast cancer

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Stella D’Oronzo ◽  
Domenica Lovero ◽  
Raffaele Palmirotta ◽  
Luigia Stefania Stucci ◽  
Marco Tucci ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Stage Iv ◽  
Metastatic Potential ◽  
Gene Variants ◽  
Primary Tumors ◽  
Mesenchymal Transition ◽  
Genomic Markers

AbstractEnumeration of circulating tumor cells (CTCs) may reflect the metastatic potential of breast cancer (BC). By using the DEPArray, we investigated CTCs with respect to their epithelial-to-mesenchymal transition phenotype and compared their genomic heterogeneity with tissue biopsies. Seventeen stage IV BC patients were enrolled. Pre-enriched CTC suspensions were stained with fluorescent-labeled antibodies to epithelial (E) and mesenchymal (M) markers. CTC samples were processed by DEPArray system and clustered in relation to their markers. DNA from CTCs, as well as from primary tumor samples, was sequenced by next generation sequencing to assess the mutational state of 50 major cancer-related genes. We identified four different CTC subsets that harbored different gene variants. The most heterogenous CTC subsets included the M+/E− phenotype, which, however, expressed only 7 repeatedly mutated genes, while in the M−/E+ subset multiple mutations affected only 2 out of 50 genes. When matching all gene variants among CTC subsets, a small number of mutations was shared by only 4 genes, namely ATM, FGFR3, PIK3CA, and TP53 that, however, were absent in primary tumors. Our results postulate that the detected mutations in all CTC subsets may be considered as genomic markers of metastatic dissemination to be investigated during early stages of BC.

Dynamic-enhanced MRI predicts metastatic potential of invasive ductal breast cancer

Breast Cancer ◽  
2002 ◽  
Vol 9 (3) ◽  
pp. 226-230 ◽  
Author(s):  
Takeshi Nagashima ◽  
Masato Suzuki ◽  
Hiroshi Yagata ◽  
Hideyuki Hashimoto ◽  
Tomotane Shishikura ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Potential ◽  
Invasive Ductal Breast Cancer ◽  
Ductal Breast Cancer ◽  
Enhanced Mri
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