Triple-negative breast cancer-derived microvesicles transfer microRNA221 to the recipient cells and thereby promote epithelial-to-mesenchymal transition Signal Transduction

The triple-negative phenotype is the most prevalent form of human breast cancer worldwide and is characterized by poor survival, high aggressiveness, and recurrence. Microvesicles (MV) are shredded plasma membrane components and critically mediate cell–cell communication, but can also induce cancer proliferation and metastasis. Previous studies have revealed that protease-activated receptor 2 (PAR2) contributes significantly to human triple-negative breast cancer (TNBC) progression by releasing nano-size MV and promoting cell proliferation, migration, and invasion. MV isolated from highly aggressive human TNBC cells impart metastatic potential to nonmetastatic cells. Over-expression of microRNA221 (miR221) has also been reported to enhance the metastatic potential of human TNBC, but miR221's relationship to PAR2-induced MV is unclear. Here, using isolated MV, immunoblotting, quantitative RT-PCR, FACS analysis, and enzymatic assays, we show that miR221 is translocated via human TNBC-derived MV, which upon fusion with recipient cells, enhance their proliferation, survival, and metastasis both in vitro and in vivo by inducing the epithelial-to-mesenchymal transition (EMT). Administration of anti-miR221 significantly impaired MV-induced expression of the mesenchymal markers Snail, Slug, N-cadherin, and vimentin in the recipient cells, whereas restoring expression of the epithelial marker E-cadherin. We also demonstrate that MV-associated miR221 targets phosphatase and tensi...
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Cell Biology Source Type: research

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ConclusionWe recommend excision of PN with atypia, concurrent cancerous lesion, or radiologic –pathologic non-concordance, and serial imaging follow up may be considered for image detected PN, less than 1 cm, with no atypia.
Source: Breast Cancer Research and Treatment - Category: Cancer & Oncology Source Type: research
AbstractWe demonstrated previously that the expression of the disaccharide, GalNAc β1 → 4GlcNAc (LacdiNAc), onN-glycans of cell surface glycoproteins in MDA-MB-231 human breast cancer cells suppresses their malignant properties such as tumor formation in nude mice. Here, we report changes in the morphological appearance and adhesive properties of two kinds of clonal cells of MDA-MB-231 cells overexpressing β4-N-acetyl-galactosaminyltransferase 4. The clonal cells exhibited a cobble stone-like shape as compared to a spindle-like shape of the mock-transfected cells and the original MDA-MB-231 cel...
Source: Histochemistry and Cell Biology - Category: Biomedical Science Source Type: research
Abstract Endogenous metabolites of amino acids and their derivatives in biosamples are frequently highlighted as the most differential metabolites in recent metabolomics studies. The method for the detection of amino acid derivatives such as N-acetyl amino acids and oligopeptides is rarely reported. We developed a rapid, high-throughput, sensitive and reliable quantitative method to simultaneously profile 40 underivatized amino acids and their derivatives including N-acetyl amino acids and oligopeptides in cell lines, based on ultra-high-performance liquid chromatography-electrospray tandem mass spectrometry (UHPL...
Source: Talanta - Category: Chemistry Authors: Tags: Talanta Source Type: research
ez Wandaliz Torres-García Maribella Domenech The paracrine interaction between tumor cells and adjacent stroma has been associated with the oncogenic activity of the Hedgehog (Hh) pathway in triple-negative breast tumors. The present study developed a model of paracrine Hh signaling and examined the impact of mesenchymal cell sources and culture modalities in the oncogenicity of the Hh pathway in breast tumor cells. Studies consisted of tumor cell monocultures and co-cultures with cancer-associated and normal fibroblasts, tumor cells that undergo epithelial–mesenchymal transition (EMT), or adipose-...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Authors: Stergiou N, Nagel J, Pektor S, Heimes AS, Jäkel J, Brenner W, Schmidt M, Miederer M, Kunz H, Roesch F, Schmitt E Abstract There is still a great unmet medical need concerning diagnosis and treatment of breast cancer which could be addressed by utilizing specific molecular targets. Tumor-associated MUC1 is expressed on over 90 % of all breast cancer entities and differs strongly from its physiological form on epithelial cells, therefore presenting a unique target for breast cancer diagnosis and antibody-mediated immune therapy. Utilizing an anti-tumor vaccine based on a synthetically prepared glycopept...
Source: International Journal of Medical Sciences - Category: Biomedical Science Tags: Int J Med Sci Source Type: research
Authors: Fenn KM, Kalinsky K Abstract Patients with metastatic triple-negative breast cancer (mTNBC) that has progressed on first-line therapy have a poor prognosis with limited therapeutic options. Sacituzumab govitecan (SG) is a novel antibody-drug conjugate (ADC) that has shown promising efficacy in mTNBC. SG is comprised of SN-38, the active metabolite of irinotecan, conjugated via a hydrolyzable linker to the humanized RS7 antibody targeting trophoblast cell surface antigen 2 (Trop-2), a glycoprotein that is expressed at high levels in many epithelial solid tumors. It has received breakthrough therapy status b...
Source: Drugs of Today - Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research
Authors: Russo J, Su Y Abstract We have characterized two highly tumorigenic and metastatic basal B TNBC cell lines, XtMCF and LmMCF, with the additional values of having the normal and early-stage counterparts of them. This model allows the study of the evolution of TNBC, and investigates molecular pathways at different stages of transformation and progression in a relatively constant genetic background. This constitutes an ideal model for developing targeted therapy in two important fields in cancer biology which are the epithelial mesenchymal transition (EMT) and cancer stem cells (CSC). PMID: 31576538 [PubMed - in process]
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
Sumaira Qayoom, Malti Kumari, Sameer Gupta, Madhumati GoelJournal of Cancer Research and Therapeutics 2019 15(5):1186-1188 Breast cancer is one of the main sources of ovarian metastasis. Diffuse sheet of lobular carcinoma cells can strongly mimic granulosa cell tumor (GCT) which itself is a rare ovarian neoplasm constituting <5% of all the ovarian neoplasms. A 55-year-old female presented with a painful lump in the right breast associated with nipple discharge for 4 months, which on radiological and cytological findings was suspicious of an epithelial malignancy. During routine work-up, a solid-cystic lesion in th...
Source: Journal of Cancer Research and Therapeutics - Category: Cancer & Oncology Authors: Source Type: research
Alveolar progenitor cells in the mammary gland are dependent on the β4 integrin. Dev Biol. 2019 Oct 03;: Authors: Walker MR, Amante JJ, Li J, Liu H, Zhu LJ, Feltri ML, Goel HL, Mercurio AM Abstract Understanding how progenitor cell function is regulated in the mammary gland is an important developmental problem that has significant implications for breast cancer. Although it had been assumed that the expression the α6β4 integrin (β4) is restricted to the basal lineage, we report that alveolar progenitor cells in the mouse mammary gland also express this integrin based on analysis ...
Source: Developmental Biology - Category: Biology Authors: Tags: Dev Biol Source Type: research
Abstract Breast cancer is one of the most common cancer types among women in which early tumor invasion leads to metastases and death. EpCAM (epithelial cellular adhesion molecule) and HER2 (human epidermal growth factor receptor 2) are two main circulating tumor cell (CTC) subsets in HER2+ breast cancer patients. In this regard, the main aim of this study is to develop and characterize a three-dimensional (3D) breast cancer tumor model composed of CTC subsets to evaluate new therapeutic strategies and drugs. For this reason, EpCAM(+) and HER2(+) sub-populations were isolated from different cell lines to es...
Source: Molecular Biology Reports - Category: Molecular Biology Authors: Tags: Mol Biol Rep Source Type: research
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