scholarly journals Mesenchymal stromal cell activation by breast cancer secretomes in bioengineered 3D microenvironments

2019 ◽  
Vol 2 (3) ◽  
pp. e201900304 ◽  
Author(s):  
Ulrich Blache ◽  
Edward R Horton ◽  
Tian Xia ◽  
Erwin M Schoof ◽  
Lene H Blicher ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Stromal Cells ◽  
Breast Cancer Cells ◽  
Cell Activation ◽  
Tumour Microenvironment ◽  
Paracrine Signalling ◽  
Organ Specific ◽  
Mcf 7

Mesenchymal stromal cells (MSCs) are key contributors of the tumour microenvironment and are known to promote cancer progression through reciprocal communication with cancer cells, but how they become activated is not fully understood. Here, we investigate how breast cancer cells from different stages of the metastatic cascade convert MSCs into tumour-associated MSCs (TA-MSCs) using unbiased, global approaches. Using mass spectrometry, we compared the secretomes of MCF-7 cells, invasive MDA-MB-231 cells, and sublines isolated from bone, lung, and brain metastases and identified ECM and exosome components associated with invasion and organ-specific metastasis. Next, we used synthetic hydrogels to investigate how these different secretomes activate MSCs in bioengineered 3D microenvironments. Using kinase activity profiling and RNA sequencing, we found that only MDA-MB-231 breast cancer secretomes convert MSCs into TA-MSCs, resulting in an immunomodulatory phenotype that was particularly prominent in response to bone-tropic cancer cells. We have investigated paracrine signalling from breast cancer cells to TA-MSCs in 3D, which may highlight new potential targets for anticancer therapy approaches aimed at targeting tumour stroma.

GD3 synthase overexpression enhances proliferation and migration of MDA-MB-231 breast cancer cells

2009 ◽  
Vol 390 (7) ◽  
Author(s):  
Aurélie Cazet ◽  
Sophie Groux-Degroote ◽  
Béatrice Teylaert ◽  
Kyung-Min Kwon ◽  
Sylvain Lehoux ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Surface ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Breast Epithelial Cell ◽  
Invasive Ductal Breast Carcinoma ◽  
Epithelial Cell Lines ◽  
And Migration ◽  
Mcf 7

Abstract The disialoganglioside GD3 is an oncofetal marker of a variety of human tumors including melanoma and neuroblastoma, playing a key role in tumor progression. GD3 and 9-O-acetyl-GD3 are overexpressed in approximately 50% of invasive ductal breast carcinoma, but no relationship has been established between disialoganglioside expression and breast cancer progression. In order to determine the effect of GD3 expression on breast cancer development, we analyzed the biosynthesis of gangliosides in several breast epithelial cell lines including MDA-MB-231, MCF-7, BT-20, T47-D, and MCF10A, by immunocytochemistry, flow cytometry, and real-time PCR. Our results show that, in comparison to tumors, cultured breast cancer cells express a limited pattern of gangliosides. Disialogangliosides were not detected in any cell line and GM3 was only observed at the cell surface of MDA-MB-231 cells. To evaluate the influence of GD3 in breast cancer cell behavior, we established and characterized MDA-MB-231 cells overexpressing GD3 synthase. We show that GD3 synthase expressing cells accumulate GD3, GD2, and GT3 at the cell surface. Moreover, GD3 synthase overexpression bypasses the need of serum for cell growth and increases cell migration. This suggests that GD3 synthase overexpression may contribute to increasing the malignant properties of breast cancer cells.

scholarly journals The SMRT Coregulator Enhances Growth of Estrogen Receptor-α-Positive Breast Cancer Cells by Promotion of Cell Cycle Progression and Inhibition of Apoptosis

Endocrinology ◽  
2014 ◽  
Vol 155 (9) ◽  
pp. 3251-3261 ◽  
Author(s):  
Julia K. Blackmore ◽  
Sudipan Karmakar ◽  
Guowei Gu ◽  
Vaishali Chaubal ◽  
Liguo Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Estrogen Receptor Α ◽  
Breast Cancer Progression ◽  
Apoptotic Genes ◽  
Mcf 7

Abstract The SMRT coregulator functions as a dual coactivator and corepressor for estrogen receptor-α (ERα) in a gene-specific manner, and in several studies its elevated expression correlates with poor outcome for breast cancer patients. A specific role of SMRT in breast cancer progression has not been elucidated, but SMRT knock-down limits estradiol-dependent growth of MCF-7 breast cancer cells. In this study, small-interfering RNA (siRNA) and short-hairpin RNA (shRNA) approaches were used to determine the effects of SMRT depletion on growth of ERα-positive MCF-7 and ZR-75–1 breast cancer cells, as well as the ERα-negative MDA-MB-231 breast cancer line. Depletion of SMRT inhibited growth of ERα-positive cells grown in monolayer but had no effect on growth of the ERα-negative cells. Reduced SMRT levels also negatively impacted the anchorage-independent growth of MCF-7 cells as assessed by soft agar colony formation assays. The observed growth inhibitions were due to a loss of estradiol-induced progression through the G1/S transition of the cell cycle and increased apoptosis in SMRT-depleted compared with control cells. Gene expression analyses indicated that SMRT inhibits apoptosis by a coordinated regulation of genes involved in apoptosis. Functioning as a dual coactivator for anti-apoptotic genes and corepressor for pro-apoptotic genes, SMRT can limit apoptosis. Together these data indicate that SMRT promotes breast cancer progression through multiple pathways leading to increased proliferation and decreased apoptosis.

scholarly journals Evidence for Enhanced Exosome Production in Aromatase Inhibitor-Resistant Breast Cancer Cells

2020 ◽  
Vol 21 (16) ◽  
pp. 5841
Author(s):  
Giuseppina Augimeri ◽  
Giusi La Camera ◽  
Luca Gelsomino ◽  
Cinzia Giordano ◽  
Salvatore Panza ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Protein Transport ◽  
Small Gtpase ◽  
Rab Gtpase ◽  
Rab Gtpases ◽  
Breast Cancers ◽  
Mcf 7

Aromatase inhibitors (AIs) represent the standard anti-hormonal therapy for post-menopausal estrogen receptor-positive breast cancer, but their efficacy is limited by the emergence of AI resistance (AIR). Exosomes act as vehicles to engender cancer progression and drug resistance. The goal of this work was to study exosome contribution in AIR mechanisms, using estrogen-dependent MCF-7 breast cancer cells as models and MCF-7 LTED (Long-Term Estrogen Deprived) subline, modeling AIR. We found that exosome secretion was significantly increased in MCF-7 LTED cells compared to MCF-7 cells. MCF-7 LTED cells also exhibited a higher amount of exosomal RNA and proteins than MCF-7 cells. Proteomic analysis revealed significant alterations in the cellular proteome. Indeed, we showed an enrichment of proteins frequently identified in exosomes in MCF-7 LTED cells. The most up-regulated proteins in MCF-7 LTED cells were represented by Rab GTPases, important vesicle transport-regulators in cancer, that are significantly mapped in “small GTPase-mediated signal transduction”, “protein transport” and “vesicle-mediated transport” Gene Ontology categories. Expression of selected Rab GTPases was validated by immunoblotting. Collectively, we evidence, for the first time, that AIR breast cancer cells display an increased capability to release exosomes, which may be associated with an enhanced Rab GTPase expression. These data provide the rationale for further studies directed at clarifying exosome’s role on endocrine therapy, with the aim to offer relevant markers and druggable therapeutic targets for the management of hormone-resistant breast cancers.

223 PROGRESSION OF BREAST CANCER WAS CAUSED BY TREATMENT WITH BENZOPHENONE-1 AND NONYL-PHENOL VIA ALTERATION OF CELL CYCLE AND METASTASIS-RELATED GENES IN A CELLULAR MODEL

2015 ◽  
Vol 27 (1) ◽  
pp. 201
Author(s):  
S.-J. In ◽  
K.-A. Hwang ◽  
S.-H. Kim ◽  
K.-C. Choi
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cyclin D1 ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Cathepsin D ◽  
Breast Cancer Cells ◽  
Negative Control ◽  
Signalling Pathway ◽  
Mcf 7

Endocrine disrupting chemicals (EDC) are defined as environmental compounds that may result in adverse health problems such as cancer proliferaition and metastasis in humans. Benzophenone-1 (2,4-dihydroxybenzophenone, BP-1) and nonyl-phenol (NP) are known as typical EDCs. They are discharged from numerous industrial products including plastics, pesticides, drugs, detergents, and cosmetics. In this study, we examined the effect of BP-1 and NP on the growth of MCF-7 human breast cancer cells expressing oestrogen receptors (ER) in comparison with E2 to assess their risk in cancer progression. In cell viability assay, BP-1 (10–5, 10–6, and 10–7 M) and NP (10–6 and 10–7 M) were determined to induce the proliferation of MCF-7 cells as well as E2 (10–9 M) was compared to a negative control treated with DMSO (P < 0.05). Next, to confirm that BP-1 and NP increase growth and metastasis of MCF-7 cells, the alterations in transcriptional and translational levels of related markers, i.e. cyclin D1, p21, and cathepsin D, were examined by reverse-transcription (RT)-PCR and Western blot assay. Cyclin D1 is a factor responsible for G1/S cell cycle transition and p21 is a potent cyclin-dependent kinase (CDK) inhibitor that arrests cell cycle in G1 phase. Cathepsin D is one of the proteases that are responsible for cancer progression and metastasis. Treatment of MCF-7 breast cancer cells with BP-1 (10–5 M) or NP (10–6 M) resulted in up-regulation of cyclin D1 and cathepsin D and down-regulation of p21 at transcriptional and translational levels as well as E2 (10–9 M) compared to a negative control treated with DMSO (P < 0.05). In addition, E2, BP-1, or NP-induced alterations of these genes were reversed by the presence of ICI 182 780 (10–8 M), an ER antagonist, suggesting that the changes in these gene expressions may be regulated by ER-dependent signalling pathway. In conclusion, these results suggest that BP-1 and NP, like E2, may accelerate the growth of MCF-7 breast cancer cells by regulating cell-cycle-related genes through ER-mediated signalling pathway. Furthermore, these EDCs can adversely affect human health by promoting cancer metastasis through the amplification of cathepsin D via ER-dependent signalling pathway.

Mechanism research on the lupeol treatment on MCF-7 breast cancer cells based on cell metabonomics

2014 ◽  
Vol 32 (3) ◽  
pp. 278
Author(s):  
Dongdong SHI ◽  
Yuanyuan KUANG ◽  
Guiming WANG ◽  
Zhangxiao PENG ◽  
Yan WANG ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Mechanism Research ◽  
Mcf 7
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