scholarly journals Rare case of invasive lobular breast cancer metastasis to the endometrium

2020 ◽  
Vol 48 (2-3) ◽  
pp. 116-118
Author(s):  
Damir Danolić ◽  
◽  
Luka Marcelić ◽  
Ilija Alvir ◽  
Ivica Mamić ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Metastasis ◽  
Metastatic Cancer ◽  
Female Genital Tract ◽  
Breast Cancer Metastasis ◽  
Breast Cancers ◽  
Endometrial Sampling ◽  
Invasive Lobular Breast Cancer ◽  
Postmenopausal Vaginal Bleeding ◽  
Female Genital

Metastases to the female genital tract from extra-genital primary cancers are uncommon and usually occur during widespread metastatic disease. Breast cancers are the most frequent primaries, predominantly the lobular type. Here, we report a case of a 55-year-old woman with breast cancer endometrial metastasis who presented with postmenopausal vaginal bleeding. We highlight the importance of endometrial sampling to confirm the diagnosis and distinguish primary from metastatic cancer of the endometrium since the treatment and prognosis of these conditions are entirely different.

scholarly journals The Activity of KIF14, Mieap, and EZR in a New Type of the Invasive Component, Torpedo-Like Structures, Predetermines the Metastatic Potential of Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1909
Author(s):  
Tatiana S. Gerashchenko ◽  
Sofia Y. Zolotaryova ◽  
Artem M. Kiselev ◽  
Liubov A. Tashireva ◽  
Nikita M. Novikov ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Cancer Metastasis ◽  
Ether Lipid ◽  
Metastatic Tumor ◽  
Metastatic Potential ◽  
Breast Cancer Metastasis ◽  
Breast Cancers ◽  
Invasive Component ◽  
Positive Expression

Intratumor morphological heterogeneity reflects patterns of invasive growth and is an indicator of the metastatic potential of breast cancer. In this study, we used this heterogeneity to identify molecules associated with breast cancer invasion and metastasis. The gene expression microarray data were used to identify genes differentially expressed between solid, trabecular, and other morphological arrangements of tumor cells. Immunohistochemistry was applied to evaluate the association of the selected proteins with metastasis. RNA-sequencing was performed to analyze the molecular makeup of metastatic tumor cells. High frequency of metastases and decreased metastasis-free survival were detected in patients either with positive expression of KIF14 or Mieap or negative expression of EZR at the tips of the torpedo-like structures in breast cancers. KIF14- and Mieap-positive and EZR-negative cells were mainly detected in the torpedo-like structures of the same breast tumors; however, their transcriptomic features differed. KIF14-positive cells showed a significant upregulation of genes involved in ether lipid metabolism. Mieap-positive cells were enriched in genes involved in mitophagy. EZR-negative cells displayed upregulated genes associated with phagocytosis and the chemokine-mediated signaling pathway. In conclusion, the positive expression of KIF14 and Mieap and negative expression of EZR at the tips of the torpedo-like structures are associated with breast cancer metastasis.

Thidiazuron suppresses breast cancer progression via targeting miR-132 and miR-202-5p/PTEN axis mediated dysregulation of PI3K/AKT signaling pathway

2020 ◽  
Author(s):  
Hairul-Islam Ibrahim ◽  
Mohammad Bani Ismail ◽  
Rebai Ben Ammar ◽  
Emad Ahmed
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Metastatic Cancer ◽  
Akt Signaling ◽  
Breast Cancer Metastasis ◽  
Akt Signaling Pathway ◽  
Stressful Environment

Chemo-resistance and metastatic disease development are the most common causes of breast cancer recurrence and death. Thidiazuron (TDZ) is a plant growth regulator, its biological role on human and animals has not been yet clarified. In the present study, we investigated the anticancer activity of this plant phytohormone on the drug resistant-triple negative breast cancer MDA-MB-231 cell line. Treatment of the breast cancer cells with TDZ (1-50 μM) caused more stressful environment and induced a significant increase in percentages of active caspases positive cells. In addition, TDZ treatment (5 and 10 μM) significantly attenuated the migration and the invasion activities of these highly metastatic cancer cells. Mechanistically, TDZ reducesd cancer progression and invasive activity through targeting miR-202-5p, which stimulatesd the expression of the phosphatase and tensin homolog (PTEN), the tumor suppressor that downregulates PI3K/AKT signaling pathway. In the meantime, TDZ treatment statistically upregulatesd the suppressor of breast cancer proliferation, miRNA-132 that is also implicated in dysregulating the TEN-AKT/the nuclear factor NFκB signaling pathway. Interestingly, our molecular docking analysis revealed potential non-covalent interaction between TDZ with AKT, PTEN and PI3K. These findings suggest that TDZ may suppresses breast cancer metastasis through targeting miRNA-132, miR-202-5p/PTEN and PI3K/AKT downstream molecules.

scholarly journals Integrating Protein-Protein Interaction Networks with Gene- Gene Co-Expression Networks improves Gene Signatures for Classifying Breast Cancer Metastasis

2011 ◽  
Vol 8 (2) ◽  
pp. 222-238 ◽  
Author(s):  
Erik van den Akker ◽  
Bas Verbruggen ◽  
Bas Heijmans ◽  
Marian Beekman ◽  
Joost Kok ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Metastasis ◽  
Gene Selection ◽  
De Novo ◽  
Tumor Development ◽  
Interaction Network ◽  
Breast Cancer Metastasis ◽  
Breast Cancers ◽  
Proteinprotein Interaction

Summary Multiple studies have illustrated that gene expression profiling of primary breast cancers throughout the final stages of tumor development can provide valuable markers for risk prediction of metastasis and disease sub typing. However, the identification of a biologically interpretable and universally shared set of markers proved to be difficult. Here, we propose a method for de novo grouping of genes by dissecting the proteinprotein interaction network into disjoint sub networks using pair wise gene expression correlation measures. We show that the obtained sub networks are functionally coherent and are consistently identified when applied on a compendium composed of six different breast cancer studies. Application of the proposed method using different integration approaches underlines the robustness of the identified sub network related to cell cycle and identifies putative new sub network markers for metastasis related to cell-cell adhesion, the proteasome complex and JUN-FOS signalling. Although gene selection with the proposed method does not directly improve upon previously reported cross study classification performances, it shows great promises for applications in data integration and result interpretation.

scholarly journals Therapy-induced senescence in normal tissue promotes breast cancer metastasis

2020 ◽  
Author(s):  
Douglas W. Perkins ◽  
Syed Haider ◽  
David Robertson ◽  
Richard Buus ◽  
Lynda O’Leary ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Normal Tissue ◽  
Systemic Chemotherapy ◽  
Cancer Metastasis ◽  
Resistance Mechanisms ◽  
Breast Cancer Metastasis ◽  
Breast Cancers ◽  
Stromal Fibroblasts

SummaryDisseminated tumour cells, particularly in ER+ breast cancers, typically exhibit a period of dormancy that renders them insensitive to targeting by chemotherapy. Additionally, chemotherapy treatment can result in normal tissue damage, including the induction of cellular senescence. Using mouse and human breast cancer models, we demonstrate that systemic chemotherapy administration results in accumulation of long-lived senescent stromal fibroblasts and promotes metastatic outgrowth. Chemotherapy-induced senescent fibroblasts upregulate a senescence associated secretory phenotype (SASP) that accelerates 3D tumour spheroid growth by stimulating mitogenic signalling. Senolytic drugs can effectively eliminate chemotherapy-induced senescent fibroblasts in vitro, but show only modest efficacy in vivo, at least in part due to the upregulation of resistance mechanisms. In conclusion, systemic chemotherapy can establish a productive microenvironment for colonisation and outgrowth of disseminated cancer cells, however, optimisation of senotherapies for effective targeting of senescent fibroblasts is required to establish them as useful additions to standard chemotherapy.

Targeting Monoacylglycerol Lipase in Triple Negative Breast Cancer Reduced Tumor-Associated Inflammation, Tumor Growth and Tumor Colonization in the Brain

2021 ◽  
Author(s):  
Othman Benchama ◽  
Sergiy Tyukhtenko ◽  
Michael S. Malamas ◽  
Mark K. Williams ◽  
Alexandros Makriyannis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Metastasis ◽  
Triple Negative ◽  
Breast Cancer Metastasis ◽  
Monoacylglycerol Lipase ◽  
Breast Cancers ◽  
Novel Treatments ◽  
The Brain

Abstract While the prevalence of breast cancer metastasis in the brain is significantly higher in triple negative breast cancers (TNBCs), there is a lack of novel and/or improved therapies for these patients. Monoacylglycerol lipase (MAGL) is a hydrolase involved in lipid metabolism that catalyzes the degradation of 2-arachidonoylglycerol (2-AG) linked to generation of pro- and anti-inflammatory molecules. Here, we targeted MAGL in TNBCs, using the selective MAGL inhibitor AM9928 (hMAGL IC50 = 9nM, with prolonged pharmacodynamic effects of 46 hours residence time). AM9928 blocked TNBC cell adhesion and transmigration across human brain microvascular endothelial cells (HBMECs) in 3D co-cultures. In addition, AM9928 inhibited the secretion of IL-6, IL-8, and VEGF-A from TNBC cells. TNBC-derived exosomes activated HBMECs resulting in secretion of elevated levels of IL-8 and VEGF, which were inhibited by AM9928. Knockdown of MAGL by siRNA or treatment with AM9928 increased the expression of the adherent junction E-cadherin, known to be regulated by MAGL. Using in vivo studies of syngeneic GFP-4T1-BrM5 mammary tumor cells, AM9928 inhibited tumor growth in the mammary fat pads and attenuated blood brain barrier (BBB) permeability changes, resulting in reduced TNBC colonization in brain. Together, these results support the potential clinical application of MAGL inhibitors as novel treatments for TNBC.

scholarly journals Gadd45g initiates embryonic stem cell differentiation and inhibits breast cell carcinogenesis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Xinbao Zhang ◽  
Yuting Li ◽  
Junxiang Ji ◽  
Xin Wang ◽  
Meng Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Metastasis ◽  
Embryonic Stem ◽  
Specific Inhibitor ◽  
Stem Cell Differentiation ◽  
Mapk Signaling ◽  
Breast Cancer Metastasis ◽  
Tumor Formation ◽  
Embryonic Stem Cell Differentiation ◽  
Breast Cancers

AbstractMany self-renewal-promoting factors of embryonic stem cells (ESCs) have been implicated in carcinogenesis, while little known about the genes that direct ESCs exit from pluripotency and regulate tumor development. Here, we show that the transcripts of Gadd45 family genes, including Gadd45a, Gadd45b, and Gadd45g, are gradually increased upon mouse ESC differentiation. Upregulation of Gadd45 members decreases cell proliferation and induces endodermal and trophectodermal lineages. In contrast, knockdown of Gadd45 genes can delay mouse ESC differentiation. Mechanistic studies reveal that Gadd45g activates MAPK signaling by increasing expression levels of the positive modulators of this pathway, such as Csf1r, Igf2, and Fgfr3. Therefore, inhibition of MAPK signaling with a MEK specific inhibitor is capable of eliminating the differentiation phenotype caused by Gadd45g upregulation. Meanwhile, GADD45G functions as a suppressor in human breast cancers. Enforced expression of GADD45G significantly inhibits tumor formation and breast cancer metastasis in mice through limitation of the propagation and invasion of breast cancer cells. These results not only expand our understanding of the regulatory network of ESCs, but also help people better treatment of cancers by manipulating the prodifferentiation candidates.

scholarly journals SNX27–retromer assembly recycles MT1-MMP to invadopodia and promotes breast cancer metastasis

2019 ◽  
Vol 219 (1) ◽  
Author(s):  
Priyanka Sharma ◽  
Sameena Parveen ◽  
Lekha V. Shah ◽  
Madhumita Mukherjee ◽  
Yannis Kalaidzidis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Metastasis ◽  
Metastatic Cancer ◽  
Metastatic Breast ◽  
Cancer Cell Line ◽  
Breast Cancer Metastasis ◽  
Sorting Nexin ◽  
The Matrix ◽  
Intracellular Compartments ◽  
Membrane Protrusions

A variety of metastatic cancer cells use actin-rich membrane protrusions, known as invadopodia, for efficient ECM degradation, which involves trafficking of proteases from intracellular compartments to these structures. Here, we demonstrate that in the metastatic breast cancer cell line MDA-MB-231, retromer regulates the matrix invasion activity by recycling matrix metalloprotease, MT1-MMP. We further found that MT2-MMP, another abundantly expressed metalloprotease, is also invadopodia associated. MT1- and MT2-MMP showed a high degree of colocalization but were located on the distinct endosomal domains. Retromer and its associated sorting nexin, SNX27, phenocopied each other in matrix degradation via selectively recycling MT1-MMP but not MT2-MMP. ITC-based studies revealed that both SNX27 and retromer could directly interact with MT1-MMP. Analysis from a publicly available database showed SNX27 to be overexpressed or frequently altered in the patients having invasive breast cancer. In xenograft-based studies, SNX27-depleted cell lines showed prolonged survival of SCID mice, suggesting a possible implication for overexpression of the sorting nexin in tumor samples.

Sign in / Sign up

Export Citation Format

Share Document