scholarly journals Identification and characterization of long non-coding RNAs as targets of mammary tumor cell proliferation and migration

2016 ◽  
Author(s):  
Sarah D Diermeier ◽  
Kung-Chi Chang ◽  
Susan M Freier ◽  
Junyan Song ◽  
Alexander Krasnitz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Mammary Tumor ◽  
Ex Vivo ◽  
Therapeutic Targets ◽  
Collective Cell Migration ◽  
Mammary Tumor Cell ◽  
Luminal B ◽  
Primary Mammary Tumor ◽  
Non Coding Rnas

Recent genome-wide studies revealed that as much as 80% of the human genome can be transcribed whereas only 2% of this RNA is translated into proteins. Non-coding transcripts can be subdivided into several groups, with long non-coding RNAs (lncRNAs) representing the largest and most diverse class. With breast cancer being the most frequent malignancy in women worldwide, we set out to investigate the potential of lncRNAs as novel therapeutic targets. By performing RNA-Seq on tumor sections and mammary organoids from MMTVPyMT and MMTV-Neu-NDL mice, modeling the luminal B and HER2/neuamplified subtypes of human breast cancer respectively, we generated a comprehensive catalog of differentially expressed lncRNAs. We identified several hundred potentially oncogenic lncRNAs that were over-expressed in a subtype specific manner as well as numerous lncRNAs up-regulated in both models. Among these lncRNA we defined a subset of 30 previously uncharacterized lncRNAs as Mammary Tumor Associated RNAs (MaTARs) and we identified human orthologs. We functionally validated the role of these MaTARs by antisense oligonucleotide (ASO) mediated knockdown in primary mammary tumor cells and 3D ex vivo organoids. Upon independent knockdown of 15 MaTARs, we observed significantly reduced cell proliferation, invasion and/or collective cell migration in a cancer-specific context. Thus, MaTARs are likely key drivers of mammary tumor progression and/or metastasis and represent promising new therapeutic targets.

scholarly journals CXCR2: A Novel Mediator of Mammary Tumor Bone Metastasis

2019 ◽  
Vol 20 (5) ◽  
pp. 1237 ◽  
Author(s):  
Bhawna Sharma ◽  
Kalyan Nannuru ◽  
Sugandha Saxena ◽  
Michelle Varney ◽  
Rakesh Singh
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Tumor Cell ◽  
Cancer Patients ◽  
Mammary Tumor ◽  
Critical Role ◽  
Breast Cancer Patients ◽  
Mammary Tumor Cell ◽  
Primary Tumors

Most breast cancer patients die due to bone metastasis. Although metastasis accounts for 5% of the breast cancer cases, it is responsible for most of the deaths. Sometimes even before the detection of a primary tumor, most of the patients have bone and lymph node metastasis. Moreover, at the time of death, breast cancer patients have the bulk of the tumor burden in their bones. Therapy options are available for the treatment of primary tumors, but there are minimal options for treating breast cancer patients who have bone metastasis. C-X-C motif chemokine receptor type 2 (CXCR2) receptor-mediated signaling has been shown to play a critical role during bone-related inflammations and its ligands C-X-C motif chemokine ligand 6 (CXCL6) and 8 (CXCL8) aid in the resorption of bone during bone metastasis. In this study, we tested the hypothesis that CXCR2 contributes to mammary tumor-induced osteolysis and bone metastasis. In the present study, we examined the role of both tumor cell-derived and host-derived CXCR2 in influencing mammary tumor cell bone metastasis. For understanding the role of tumor cell-derived CXCR2, we utilized Cl66 CXCR2 knockdown (Cl66-shCXCR2) and Cl66-Control cells (Cl66-Control) and observed a significant decrease in tumor growth and tumor-induced osteolysis in Cl66-shCXCR2 cells in comparison with the Cl66-Control cells. Next, for understanding the role of host-derived CXCR2, we utilized mice with genomic knockdown of CXCR2 (Cxcr2−/−) and injected Cl66-Luciferase (Cl66-Luc) or 4T1-Luciferase (4T1-Luc) cells. We observed decreased bone destruction and metastasis in the bone of Cxcr2−/− mice. Our data suggest the importance of both tumor cell- and host-derived CXCR2 signaling in the bone metastasis of breast cancer cells.

scholarly journals The CXCL5/CXCR2 axis is sufficient to promote breast cancer colonization during bone metastasis

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Ricardo Romero-Moreno ◽  
Kimberly J. Curtis ◽  
Thomas R. Coughlin ◽  
Maria Cristina Miranda-Vergara ◽  
Shourik Dutta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Bone Metastasis ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Ex Vivo ◽  
Metastatic Cancer ◽  
Culture Method ◽  
Cancer Cell Proliferation ◽  
Promote Breast Cancer

Abstract Bone is one of the most common sites for metastasis across cancers. Cancer cells that travel through the vasculature and invade new tissues can remain in a non-proliferative dormant state for years before colonizing the metastatic site. Switching from dormancy to colonization is the rate-limiting step of bone metastasis. Here we develop an ex vivo co-culture method to grow cancer cells in mouse bones to assess cancer cell proliferation using healthy or cancer-primed bones. Profiling soluble factors from conditioned media identifies the chemokine CXCL5 as a candidate to induce metastatic colonization. Additional studies using CXCL5 recombinant protein suggest that CXCL5 is sufficient to promote breast cancer cell proliferation and colonization in bone, while inhibition of its receptor CXCR2 with an antagonist blocks proliferation of metastatic cancer cells. This study suggests that CXCL5 and CXCR2 inhibitors may have efficacy in treating metastatic bone tumors dependent on the CXCL5/CXCR2 axis.

Green tea extracts decrease carcinogen-induced mammary tumor burden in rats and rate of breast cancer cell proliferation in culture

2001 ◽  
Vol 82 (3) ◽  
pp. 387-398 ◽  
Author(s):  
Kathryn T. Kavanagh ◽  
Laurie J. Hafer ◽  
Dong W. Kim ◽  
Koren K. Mann ◽  
David H. Sherr ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Green Tea ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Mammary Tumor ◽  
Tumor Burden ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation

scholarly journals Phase II Randomized Preoperative Window-of-Opportunity Study of the PI3K Inhibitor Pictilisib Plus Anastrozole Compared With Anastrozole Alone in Patients With Estrogen Receptor–Positive Breast Cancer

2016 ◽  
Vol 34 (17) ◽  
pp. 1987-1994 ◽  
Author(s):  
Peter Schmid ◽  
Sarah E. Pinder ◽  
Duncan Wheatley ◽  
Jane Macaskill ◽  
Charles Zammit ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Estrogen Receptor ◽  
Geometric Mean ◽  
Tumor Cell Proliferation ◽  
Geometric Mean Ratio ◽  
Ki 67 ◽  
Luminal B ◽  
Estrogen Receptor Positive ◽  
Positive Breast Cancer

Purpose Preclinical data support a key role for the PI3K pathway in estrogen receptor–positive breast cancer and suggest that combining PI3K inhibitors with endocrine therapy may overcome resistance. This preoperative window study assessed whether adding the PI3K inhibitor pictilisib (GDC-0941) can increase the antitumor effects of anastrozole in primary breast cancer and aimed to identify the most appropriate patient population for combination therapy. Patients and Methods In this randomized, open-label phase II trial, postmenopausal women with newly diagnosed operable estrogen receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative breast cancers were recruited. Participants were randomly allocated (2:1, favoring the combination) to 2 weeks of preoperative treatment with anastrozole 1 mg once per day (n = 26) or the combination of anastrozole 1 mg with pictilisib 260 mg once per day (n = 49). The primary end point was inhibition of tumor cell proliferation as measured by change in Ki-67 protein expression between tumor samples taken before and at the end of treatment. Results There was significantly greater geometric mean Ki-67 suppression of 83.8% (one-sided 95% CI, ≥ 79.0%) for the combination and 66.0% (95% CI, ≤ 75.4%) for anastrozole (geometric mean ratio [combination:anastrozole], 0.48; 95% CI, ≤ 0.72; P = .004). PIK3CA mutations were not predictive of response to pictilisib, but there was significant interaction between response to treatment and molecular subtype (P = .03); for patients with luminal B tumors, the combination:anastrozole geometric mean ratio of Ki-67 suppression was 0.37 (95% CI, ≤ 0.67; P = .008), whereas no significant Ki-67 response was observed for pictilisib in luminal A tumors (1.01; P = .98). Multivariable analysis confirmed Ki-67 response to the combination treatment of patients with luminal B tumors irrespective of progesterone receptor status or baseline Ki-67 expression. Conclusion Adding pictilisib to anastrozole significantly increases suppression of tumor cell proliferation in luminal B primary breast cancer.

scholarly journals Long non-coding RNAs as monitoring tools and therapeutic targets in breast cancer

2018 ◽  
Vol 42 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Mª Luisa Pecero ◽  
Javier Salvador-Bofill ◽  
Sonia Molina-Pinelo
Keyword(s):  
Breast Cancer ◽  
Therapeutic Targets ◽  
Monitoring Tools ◽  
Non Coding Rnas

scholarly journals Breast Cancer and the Other Non-Coding RNAs

2021 ◽  
Vol 22 (6) ◽  
pp. 3280
Author(s):  
Dana Dvorská ◽  
Dušan Braný ◽  
Marcela Ňachajová ◽  
Erika Halašová ◽  
Zuzana Danková
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Breast Cancer Cell Lines ◽  
Altered Expression ◽  
Factors Affecting ◽  
Mesenchymal Transition ◽  
Non Coding Rnas ◽  
Endothelial To Mesenchymal Transition ◽  
Molecular Therapeutic

Breast cancer is very heterogenous and the most common gynaecological cancer, with various factors affecting its development. While its impact on human lives and national health budgets is still rising in almost all global areas, many molecular mechanisms affecting its onset and development remain unclear. Conventional treatments still prove inadequate in some aspects, and appropriate molecular therapeutic targets are required for improved outcomes. Recent scientific interest has therefore focused on the non-coding RNAs roles in tumour development and their potential as therapeutic targets. These RNAs comprise the majority of the human transcript and their broad action mechanisms range from gene silencing to chromatin remodelling. Many non-coding RNAs also have altered expression in breast cancer cell lines and tissues, and this is often connected with increased proliferation, a degraded extracellular environment, and higher endothelial to mesenchymal transition. Herein, we summarise the known abnormalities in the function and expression of long non-coding RNAs, Piwi interacting RNAs, small nucleolar RNAs and small nuclear RNAs in breast cancer, and how these abnormalities affect the development of this deadly disease. Finally, the use of RNA interference to suppress breast cancer growth is summarised.

scholarly journals Stable Differences in Intrinsic Mitochondrial Membrane Potential of Tumor Cell Subpopulations Reflect Phenotypic Heterogeneity

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Michele A. Houston ◽  
Leonard H. Augenlicht ◽  
Barbara G. Heerdt
Keyword(s):  
Membrane Potential ◽  
Tumor Cell ◽  
Disease Progression ◽  
Mitochondrial Membrane Potential ◽  
Mammary Tumor ◽  
Mitochondrial Membrane ◽  
Cell Populations ◽  
Mammary Tumor Cell ◽  
Colonic Tumor ◽  
Primary Mammary Tumor

Heterogeneity among cells that constitute a solid tumor is important in determining disease progression. Our previous work established that, within a population of metastatic colonic tumor cells, there are minor subpopulations of cells with stable differences in their intrinsic mitochondrial membrane potential (ΔΨm), and that these differences in ΔΨm are linked to tumorigenic phenotype. Here we expanded this work to investigate primary mammary, as well as colonic, tumor cell lines. We show that within a primary mammary tumor cell population, and in both primary and metastatic colonic tumor cell populations, there are subpopulations of cells with significant stable variations in intrinsic ΔΨm. In each of these 3 tumor cell populations, cells with relatively higher intrinsic ΔΨm exhibit phenotypic properties consistent with promotion of tumor cell survival and expansion. However, additional properties associated with invasive potential appear in cells with higher intrinsic ΔΨm only from the metastatic colonic tumor cell line. Thus, it is likely that differences in the intrinsic ΔΨm among cells that constitute primary mammary tumor populations, as well as primary and metastatic colonic tumor populations, are markers of an acquired tumor phenotype which, within the context of the tumor, influence the probability that particular cells will contribute to disease progression.

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