scholarly journals Expression of CCL2/CCR2 signaling proteins in breast carcinoma cells is associated with invasive progression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wei Bin Fang ◽  
Diana Sofia Acevedo ◽  
Curtis Smart ◽  
Brandon Zinda ◽  
Nadia Alissa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Invasive Breast Cancer ◽  
Ductal Carcinoma ◽  
Early Stage ◽  
Breast Cancer Cell Lines ◽  
Breast Epithelial Cell ◽  
Epithelial Cell Line ◽  
Signaling Proteins ◽  
Breast Epithelial

AbstractDuctal carcinoma in situ (DCIS) is the most common type of pre-invasive breast cancer diagnosed in women. Because the majority of DCIS cases are unlikely to progress to invasive breast cancer, many women are over-treated for DCIS. By understanding the molecular basis of early stage breast cancer progression, we may identify better prognostic factors and design treatments tailored specifically to the predicted outcome of DCIS. Chemokines are small soluble molecules with complex roles in inflammation and cancer progression. Previously, we demonstrated that CCL2/CCR2 chemokine signaling in breast cancer cell lines regulated growth and invasion through p42/44MAPK and SMAD3 dependent mechanisms. Here, we sought to determine the clinical and functional relevance of CCL2/CCR2 signaling proteins to DCIS progression. Through immunostaining analysis of DCIS and IDC tissues, we show that expression of CCL2, CCR2, phospho-SMAD3 and phospho-p42/44MAPK correlate with IDC. Using PDX models and an immortalized hDCIS.01 breast epithelial cell line, we show that breast epithelial cells with high CCR2 and high CCL2 levels form invasive breast lesions that express phospho-SMAD3 and phospho-p42/44MAPK. These studies demonstrate that increased CCL2/CCR2 signaling in breast tissues is associated with DCIS progression, and could be a signature to predict the likelihood of DCIS progression to IDC.

scholarly journals Molecular and Cellular Characterization of Two Patient-Derived Ductal Carcinoma in Situ (DCIS) Cell Lines, ETCC-006 and ETCC-010

2020 ◽  
Author(s):  
Julia Samson ◽  
Kellie Dean
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Line ◽  
Cell Lines ◽  
Ductal Carcinoma ◽  
Breast Cancer Cell Lines ◽  
Breast Epithelial Cell ◽  
Anchorage Independent Growth

Abstract Background: Currently it is unclear how in situ breast cancer progresses to invasive disease; therefore, a better understanding of the events that occur during the transition to invasive carcinoma is warranted. Here we have conducted a detailed molecular and cellular characterization of two, patient-derived, ductal carcinoma in situ (DCIS) cell lines, ETCC-006 and ETCC-010. Methods: Human DCIS cell lines, ETCC-006 and ETCC-010, were compared against a panel of cell lines including the immortalized, breast epithelial cell line, MCF10A, breast cancer cell lines, MCF7 and MDA-MB-231, and another DCIS line, MCF10DCIS.com. Cell morphology, hormone and HER2/ERBB2 receptor status, cell proliferation, survival, migration, anchorage-independent growth, indicators of EMT, cell signalling pathways and cell cycle proteins were examined using immunostaining, immunoblots, and quantitative, reverse transcriptase PCR (qRT-PCR), along with clonogenic, wound-closure and soft agar assays. RNA sequencing (RNAseq) was used to provide a transcriptomic profile. Results: ETCC-006 and ETCC-010 cells displayed notable differences to another DCIS cell line, MCF10DCIS.com, in terms of morphology, steroid-receptor/HER status and markers of EMT. The ETCC cell lines lack ER/PR and HER, form colonies in clonogenic assays, have migratory capacity and are capable of anchorage-independent growth. Despite being isogenic, less than 30% of differentially expressed transcripts overlapped between the two lines, with enrichment in receptor tyrosine kinase pathways and DNA replication/cell cycle programs. Conclusions: For the first time, we provide a molecular and cellular characterization of two, patient-derived DCIS cell lines, ETCC-006 and ETCC-010, facilitating future investigations into the molecular basis of DCIS to invasive ductal carcinoma transition.

scholarly journals Extracellular vesicles from young women’s breast cancer patients drive increased invasion of non-malignant cells via the Focal Adhesion Kinase pathway: a proteomic approach

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Kimberly R. Jordan ◽  
Jessica K. Hall ◽  
Troy Schedin ◽  
Michelle Borakove ◽  
Jenny J. Xian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Focal Adhesion ◽  
Invasive Breast Cancer ◽  
Breast Cancer Cells ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Non Invasive ◽  
Healthy Donors

Abstract Background Extracellular vesicles (EVs) are small membrane particles that contribute to cancer progression and metastases by transporting biologically significant proteins and nucleic acids. They may also serve as biomarkers of various disease states or important therapeutic targets. Breast cancer EVs have the potential to change the behavior of other cells in their microenvironment. However, the proteomic content of EVs isolated from young women’s breast cancer patients and the mechanisms underlying the influence of EVs on tumor cell behavior have not yet been reported. Methods In our current translational studies, we compared the proteomic content of EVs isolated from invasive breast cancer cell lines and plasma samples from young women’s breast cancer (YWBC) patients and age-matched healthy donors using mass spectrometry. We analyzed the functionality of EVs in two dimensional tumor cell invasion assays and the gene expression changes in tumor cells after incubation with EVs. Results We found that treatment with EVs from both invasive breast cancer cell lines and plasma of YWBC patients altered the invasive properties of non-invasive breast cancer cells. Proteomics identified differences between EVs from YWBC patients and healthy donors that correlated with their altered function. Further, we identified gene expression changes in non-invasive breast cancer cells after treatment with EVs that implicate the Focal Adhesion Kinase (FAK) signaling pathway as a potential targetable pathway affected by breast cancer-derived EVs. Conclusions Our results suggest that the proteome of EVs from breast cancer patients reflects their functionality in tumor motility assays and may help elucidate the role of EVs in breast cancer progression.

Prediction Model For Extensive Ductal Carcinoma In Situ Around Early-Stage Invasive Breast Cancer

2016 ◽  
Vol 51 (7) ◽  
pp. 462-468 ◽  
Author(s):  
Floortje M. Knuttel ◽  
Bas H.M. van der Velden ◽  
Claudette E. Loo ◽  
Sjoerd G. Elias ◽  
Jelle Wesseling ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prediction Model ◽  
Ductal Carcinoma In Situ ◽  
Invasive Breast Cancer ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Early Stage

scholarly journals MicroRNA-205-5p inhibits three-dimensional spheroid proliferation of ErbB2-overexpressing breast epithelial cells through direct targeting of CLCN3

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7799 ◽  
Author(s):  
Takayoshi Takeno ◽  
Takuya Hasegawa ◽  
Hiroki Hasegawa ◽  
Yasuyuki Ueno ◽  
Ryo Hamataka ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cellular Proliferation ◽  
Rna Binding ◽  
Three Dimensional ◽  
Luciferase Reporter ◽  
Breast Epithelial Cell ◽  
Epithelial Cell Line ◽  
Shrna Expression ◽  
Direct Target ◽  
Breast Epithelial

We previously reported that microRNA-205-5p (miR-205-5p) is significantly decreased in the ErbB2-overexpressing breast epithelial cell line MCF10A-ErbB2 compared with control cells. In this study, we identified a direct target of miR-205-5p, chloride voltage-gated channel 3 (CLCN3). CLCN3 expression was induced by ErbB2 overexpression; this induced expression was then reduced to control levels by the transfection of the miR-205-5p precursor. In RNA-binding protein immunoprecipitation with Ago1/2/3 antibody, CLCN3 was significantly enriched in 293T embryonic kidney cells with miR-205-5p mimic transfection compared with negative control mimic transfection. In luciferase reporter assays using CLCN3 3′-UTR constructs, the miR-205-5p mimic significantly decreased reporter activity of both wild-type and partial mutant constructs in MCF10A-ErbB2 cells. In contrast, no inhibitory effects of the miR-205-5p mimic were detected using the complete mutant constructs. Since miR-205-5p expression in exosomes derived from MCF10A-neo cells was substantially higher than in exosomes derived from MCF10A-ErbB2 cells, we next investigated whether an exosome-mediated miR-205-5p transfer could control CLCN3 expression. To this end, exosomal miR-205-5p derived from MCF10A-neo cells was functionally transferred to MCF10A-ErbB2 cells, which served to decrease the expression of CLCN3. To assess the roles of CLCN3 in breast cancer, we next performed three-dimensional (3D) spheroid proliferation analyses using MCF10A-ErbB2 cells treated with MCF10A-neo-derived exosomes or CLCN3 shRNA stably expressing SKBR3 and MDA-MB-453 breast cancer cells. Our results showed that both treatment with MCF10A-neo-derived exosome and CLCN3 shRNA expression suppressed 3D spheroid proliferation. Collectively, these novel findings suggest that CLCN3 may be a novel direct target of miR-205-5p and this CLCN3/miR-205-5p interaction may serve a pivotal role in regulating breast cancer cellular proliferation under physiological conditions.

scholarly journals Severe depression more common in patients with ductal carcinoma in situ than early-stage invasive breast cancer patients

2017 ◽  
Vol 167 (1) ◽  
pp. 205-213 ◽  
Author(s):  
M. L. Gregorowitsch ◽  
H. J. G. D. van den Bongard ◽  
D. A. Young-Afat ◽  
J. P. Pignol ◽  
C. H. van Gils ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Ductal Carcinoma In Situ ◽  
Invasive Breast Cancer ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Early Stage ◽  
Severe Depression ◽  
Breast Cancer Patients

scholarly journals Analysis of Key Radiographic Characteristics of Early Invasive Breast Cancer, Stages T₁ₐ₋bN₀M₀ and DCIS

2021 ◽  
Vol 4 (1) ◽  
pp. 9-19
Author(s):  
G. S. Alieva ◽  
G. P. Korzhenkova ◽  
I. V. Kolyadina
Keyword(s):  
Breast Cancer ◽  
Ductal Carcinoma In Situ ◽  
Invasive Breast Cancer ◽  
Carcinoma In Situ ◽  
World Literature ◽  
Ductal Carcinoma ◽  
Early Stage ◽  
Malignant Neoplasm ◽  
Morphological Examination

Relevance: The systematization of radiological signs of microcarcinomas will increase the frequency of detection of the disease at an early stage and maximize the effectiveness of breast cancer treatment.Purpose: To assess the key radiological characteristics of early forms of breast cancer (invasive tumors up to 1.0 cm and ductal carcinoma in situ).Material and methods: The key radiological characteristics were studied in 110 patients with verified early forms of breast cancer: ductal carcinoma in situ (DCIS), invasive breast cancer up to 1 cm in size according to the morphological examination of the surgical material in the absence of signs of regional and distant metastasis — stage p T₁ₐ₋bN₀M₀.Results: The main radiological signs detected in mammography (MG) in early breast cancer were the nodular mass without microcalcifications — in 26 cases (23.9 %), the nodule and microcalcifications — in 35 cases (32.1 %), in 27 patients (24.8 %) — microcalcifications without a tumor node. In addition, in 17 cases (15.6 %) there was a violation of the architectonics or focal asymmetry, and in 4 patients (3.7 %) no signs of a malignant process were revealed at all with MG. The revealed changes in the breast in most patients (83 cases, 76.1 %) were interpreted as BIRADS 5, which indicates an extremely high probability of the presence of a malignant neoplasm. In 9 cases (8.3 %) after mammography, the diagnosis was interpreted as BIRADS 4, in 16 (14.7 %) cases the category BIRADS 0 was assigned, which required additional examination methods, and only in 1 patient (0.9 %) the revealed changes were interpreted as benign.Conclusions: Mammography performed in 92 patients (84.4 %), based on the assessment of radiological signs, to establish the BIRADS 4/5 category, which served as the basis for performing a biopsy and verifying the diagnosis. However, in 15 % there were diagnostic difficulties in interpreting the data, which confirms the data of the world literature on the complexity of the differential diagnosis of microcarcinomas. 

scholarly journals Transition to invasive breast cancer is associated with progressive changes in the structure and composition of tumor stroma

2021 ◽  
Author(s):  
Tyler Risom ◽  
David R Glass ◽  
Candace C Liu ◽  
Belén Rivero-Gutiérrez ◽  
Alex Baranski ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Invasive Breast Cancer ◽  
Ductal Carcinoma ◽  
Ion Beam ◽  
Tumor Stroma ◽  
Cell Segmentation ◽  
Learning Tools ◽  
Full Spectrum ◽  
Antibody Staining

AbstractDuctal carcinoma in situ (DCIS) is a pre-invasive lesion that is thought to be a precursor to invasive breast cancer (IBC). To understand how the tumor microenvironment (TME) changes with transition to IBC, we used Multiplexed Ion Beam Imaging by time of flight (MIBI-TOF) and a 37-plex antibody staining panel to analyze 140 clinically annotated surgical resections covering the full spectrum of breast cancer progression. We compared normal, DCIS, and IBC tissues using machine learning tools for multiplexed cell segmentation, pixel-based clustering, and object morphometrics. Transition from DCIS to IBC was found to occur along a trajectory marked by coordinated shifts in location and function of myoepithelium, fibroblasts, and infiltrating immune cells in the surrounding stroma. Taken together, this comprehensive study within the HTAN Breast PreCancer Atlas offers insight into the etiologies of DCIS, its transition to IBC, and emphasizes the importance of the TME stroma in promoting these processes.

scholarly journals LINC00885 a Novel Oncogenic Long Non-Coding RNA Associated with Early Stage Breast Cancer Progression

2020 ◽  
Vol 21 (19) ◽  
pp. 7407
Author(s):  
Martin C. Abba ◽  
Romina Canzoneri ◽  
Agustina Gurruchaga ◽  
Jaeho Lee ◽  
Pradeep Tatineni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathways ◽  
Cancer Progression ◽  
Ductal Carcinoma ◽  
Early Stage ◽  
Breast Cancer Progression ◽  
Early Stage Breast Cancer ◽  
Protein Coding ◽  
Breast Cells ◽  
Invasive Breast Carcinomas

Long intergenic non-protein coding RNA 885 (LINC00885) was identified as significantly upregulated in breast ductal carcinoma in situ (DCIS). The aim of this study was to characterize the phenotypic effects and signaling pathways modulated by LINC00885 in non-invasive and invasive breast cancer models. We determined that LINC00885 induces premalignant phenotypic changes by increasing cell proliferation, motility, migration and altering 3D growth in normal and DCIS breast cell lines. Transcriptomic studies (RNA-seq) identified the main signaling pathways modulated by LINC00885, which include bioprocesses related to TP53 signaling pathway and proliferative signatures such as activation of EREG, EGFR and FOXM1 pathways. LINC00885 silencing in breast cancer lines overexpressing this lncRNA leads to downregulation of proliferation related transcripts such as EREG, CMYC, CCND1 and to significant decrease in cell migration and motility. TCGA-BRCA data analyses show an association between high LINC00885 expression and worse overall survival in patients with primary invasive breast carcinomas (p = 0.024), suggesting that the pro-tumorigenic effects of LINC00885 overexpression persist post-invasion. We conclude that LINC00885 behaves as a positive regulator of cell growth both in normal and DCIS breast cells possibly operating as a ceRNA and representing a novel oncogenic lncRNA associated with early stage breast cancer progression.

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