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Breast Cancer Cancer associated Fibroblast

Caitlin E Jones, Anisha M Hammer, YouJin Cho, Gina M Sizemore, Edna Cukierman, Lisa D Yee, Samir N Ghadiali, Michael C Ostrowski, Jennifer L Leight
The organization of the extracellular matrix has a profound impact on cancer development and progression. The matrix becomes aligned throughout tumor progression, providing "highways" for tumor cell invasion. Aligned matrix is associated with breast density and is a negative prognostic factor in several cancers; however, the underlying mechanisms regulating this reorganization remain poorly understood. Deletion of the tumor suppressor Pten in the stroma was previously shown to promote extracellular matrix expansion and tumor progression...
December 11, 2018: Neoplasia: An International Journal for Oncology Research
Yongfang Xie, Mingling Wang, Min Cheng, Zhiqin Gao, Guohui Wang
The purpose of this study was to investigate the viscoelastic behaviors of cancer cells and normal cells using the micropipette aspiration technique combined with the standard linear viscoelastic solid model. The viscoelastic behaviors of pairs of cell lines (human skin cells and human skin cancer cells, human fetal lung fibroblasts and human lung cancer cells, human mammary fibroblasts and human breast cancer cells, and human hepatocyte cells and human hepatocellular carcinoma cells) were tested by the micropipette aspiration technique...
November 30, 2018: Journal of the Mechanical Behavior of Biomedical Materials
Xinyi Wang, Jing Ai, Hongyan Liu, Xia Peng, Hui Chen, Yi Chen, Yi Su, Aijun Shen, Xun Huang, Jian Ding, Meiyu Geng
Acquired resistance severely hinders the application of small molecule inhibitors. Our understanding of acquired resistance related to fibroblast growth factor receptors (FGFRs) is limited. Here, to explore the underlying mechanism of acquired resistance in FGFR-aberrant cancer cells, we generated cells resistant to multiple FGFR inhibitors and investigated the potential mechanisms underlying acquired resistance. We discovered that reprogramming of the secretome is closely associated with acquired resistance to FGFR inhibitors...
December 6, 2018: Molecular Cancer Therapeutics
Michael Bartoschek, Nikolay Oskolkov, Matteo Bocci, John Lövrot, Christer Larsson, Mikael Sommarin, Chris D Madsen, David Lindgren, Gyula Pekar, Göran Karlsson, Markus Ringnér, Jonas Bergh, Åsa Björklund, Kristian Pietras
Cancer-associated fibroblasts (CAFs) are a major constituent of the tumor microenvironment, although their origin and roles in shaping disease initiation, progression and treatment response remain unclear due to significant heterogeneity. Here, following a negative selection strategy combined with single-cell RNA sequencing of 768 transcriptomes of mesenchymal cells from a genetically engineered mouse model of breast cancer, we define three distinct subpopulations of CAFs. Validation at the transcriptional and protein level in several experimental models of cancer and human tumors reveal spatial separation of the CAF subclasses attributable to different origins, including the peri-vascular niche, the mammary fat pad and the transformed epithelium...
December 4, 2018: Nature Communications
Zhuo Chen, Lin-Jiang Tong, Bai-You Tang, Hong-Yan Liu, Xin Wang, Tao Zhang, Xian-Wen Cao, Yi Chen, Hong-Lin Li, Xu-Hong Qian, Yu-Fang Xu, Hua Xie, Jian Ding
The fibroblast growth factor receptors (FGFRs) are increasingly considered attractive targets for therapeutic cancer intervention due to their roles in tumor metastasis and angiogenesis. Here, we identified a new selective FGFR inhibitor, C11, and assessed its antitumor activities. C11 was a selective FGFR1 inhibitor with an IC50 of 19 nM among a panel of 20 tyrosine kinases. C11 inhibited cell proliferation in various tumors, particularly bladder cancer and breast cancer. C11 also inhibited breast cancer MDA-MB-231 cell migration and invasion via suppression of FGFR1 phosphorylation and its downstream signaling pathway...
November 28, 2018: Acta Pharmacologica Sinica
Jose M Ayuso, Amani Gillette, Karina Lugo-Cintrón, Suehelay Acevedo-Acevedo, Ismael Gomez, Molly Morgan, Tiffany Heaster, Kari B Wisinski, Sean P Palecek, Melissa C Skala, David J Beebe
BACKGROUND: Ductal carcinoma in situ (DCIS) is the earliest stage of breast cancer. During DCIS, tumor cells remain inside the mammary duct, growing under a microenvironment characterized by hypoxia, nutrient starvation, and waste product accumulation; this harsh microenvironment promotes genomic instability and eventually cell invasion. However, there is a lack of biomarkers to predict what patients will transition to a more invasive tumor or how DCIS cells manage to survive in this harsh microenvironment...
October 25, 2018: EBioMedicine
Huan Cao, Melissa Kao Hui Lee, Haibo Yang, Siu Kwan Sze, Nguan Soon Tan, Chor Yong Tay
Tumor stromal residing cancer-associated fibroblasts (CAFs) are significant accomplices in the growth and development of malignant neoplasm. As cancer progresses, the stroma undergoes a dramatic remodeling and stiffening of its extracellular matrix (ECM). However, exactly how these biomechanical changes influence CAF behavior and the functional paracrine crosstalk with the neighboring tumor cells in a 3-dimensional (3D) microenvironment remains elusive. Herein, a collagen and alginate interpenetrating network (CoAl-IPN) hydrogel system was employed as a 3D in vitro surrogate of the cancerous breast tissue stromal niche...
November 27, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
Yuyuan Yao, Qinglong Guo, Yue Cao, Yangmin Qiu, Renxiang Tan, Zhou Yu, Yuxin Zhou, Na Lu
BACKGROUND: Cancer-associated fibroblasts (CAFs) are activated fibroblasts associated with cancer. They have an important role in tumor growth and metastasis. Artemisinin (ART) is a sesquiterpene lactone extracted from Chinese herb qinghao, and artemether (ARM), artesunate (ARS) and dihydroartemisinin (DHA) were synthesized derivatives of artemisinin, which also have anti-malarial and anti-cancer effects such as artemisinin. METHODS: In this study, we investigated the in-vitro and in-vivo effects of artemisinin derivatives on inactivating cancer-associated fibroblasts and uncovered its underlying mechanism...
November 26, 2018: Journal of Experimental & Clinical Cancer Research: CR
Guoming Hu, Shimin Wang, Feng Xu, Qiannan Ding, Wei Chen, Kefang Zhong, Liming Huang, Qi Xu
BACKGROUND/AIMS: Tumor-infiltrating fibroblasts are a heterogeneous population, and different subpopulations play differential roles in tumor microenvironment. However, the prognostic role of podoplanin+ fibroblasts in human solid tumors still remains controversial. Therefore, we performed the meta-analysis to better understand the role of this subpopulation in prognosis prediction for patients with solid tumor. METHODS: We searched PubMed and EBSCO to identify the studies evaluating the association of intratumoral podoplanin+ fibroblast density detected by immunohistochemical method and overall survival (OS) and/or disease-free survival (DFS) in patients with solid tumor, then computed extracted data into hazard ratios for OS, DFS and clinicopathological features with STATA 12...
November 26, 2018: Cellular Physiology and Biochemistry
Yael Raz, Noam Cohen, Ophir Shani, Rachel E Bell, Sergey V Novitskiy, Lilach Abramovitz, Carmit Levy, Michael Milyavsky, Leonor Leider-Trejo, Harold L Moses, Dan Grisaru, Neta Erez
Cancer-associated fibroblasts (CAFs) are highly prominent in breast tumors, but their functional heterogeneity and origin are still largely unresolved. We report that bone marrow (BM)-derived mesenchymal stromal cells (MSCs) are recruited to primary breast tumors and to lung metastases and differentiate to a distinct subpopulation of CAFs. We show that BM-derived CAFs are functionally important for tumor growth and enhance angiogenesis via up-regulation of Clusterin. Using newly generated transgenic mice and adoptive BM transplantations, we demonstrate that BM-derived fibroblasts are a substantial source of CAFs in the tumor microenvironment...
November 23, 2018: Journal of Experimental Medicine
J M Houthuijzen, J Jonkers
Tumor cells exist in close proximity with non-malignant cells. Extensive and multilayered crosstalk between tumor cells and stromal cells tailors the tumor microenvironment (TME) to support survival, growth, and metastasis. Fibroblasts are one of the largest populations of non-malignant host cells that can be found within the TME of breast, pancreatic, and prostate tumors. Substantial scientific evidence has shown that these cancer-associated fibroblasts (CAFs) are not only associated with tumors by proximity but are also actively recruited to developing tumors where they can influence other cells of the TME as well as influencing tumor cell survival and metastasis...
November 21, 2018: Cancer Metastasis Reviews
Min Yao, Wei Fang, Curtis Smart, Qingting Hu, Shixia Huang, Nehemiah Alvarez, Patrick Fields, Nikki Cheng
Basal-like breast cancers are an aggressive breast cancer subtype, which often lack estrogen receptor, progesterone receptor and Her2 expression, and are resistant to anti-hormonal and targeted therapy, resulting in few treatment options. Understanding the underlying mechanisms that regulate progression of basal-like breast cancers would lead to new therapeutic targets and improved treatment strategies. Breast cancer progression is characterized by inflammatory responses, regulated in part by chemokines. The CCL2/CCR2 chemokine pathway is best known for regulating breast cancer progression through macrophage dependent mechanisms...
November 16, 2018: Molecular Cancer Research: MCR
Adele Vivacqua, Anna Sebastiani, Anna Maria Miglietta, Damiano Cosimo Rigiracciolo, Francesca Cirillo, Giulia Raffaella Galli, Marianna Talia, Maria Francesca Santolla, Rosamaria Lappano, Francesca Giordano, Maria Luisa Panno, Marcello Maggiolini
Estrogens acting through the classic estrogen receptors (ERs) and the G protein estrogen receptor (GPER) regulate the expression of diverse miRNAs, small sequences of non-coding RNA involved in several pathophysiological conditions, including breast cancer. In order to provide novel insights on miRNAs regulation by estrogens in breast tumor, we evaluated the expression of 754 miRNAs by TaqMan Array in ER-negative and GPER-positive SkBr3 breast cancer cells and cancer-associated fibroblasts (CAFs) upon 17β-estradiol (E2) treatment...
November 9, 2018: Cells
Mysoon M Al-Ansari, Abdelilah Aboussekhra
The ATR protein kinase is a master regulator of the cellular responses to DNA damage and replication stresses. Despite these crucial physiological roles, the implication of ATR in human carcinogenesis remains elusive. We have shown here that the ATR level is reduced in most cancer-associated fibroblasts (CAFs) as compared to their adjacent normal counterparts. Importantly, specific ATR knockdown activated breast fibroblasts, and enhanced their paracrine pro-carcinogenic effects via strong increase in the expression/secretion of SDF-1 and IL-6...
October 5, 2018: Oncotarget
Guoming Hu, Feng Xu, Kefang Zhong, Shimin Wang, Liming Huang, Wei Chen
Purpose: Activated tumor-infiltrating fibroblasts were significantly associated with survival of cancer patients. However, they are heterogeneous population, and the prognostic role of these cells in human breast cancer still remains controversial. Herein, we performed the meta-analysis to better understand the role of these cells in prognosis prediction for breast cancer patients. Methods: We searched PubMed and EBSCO to identify the studies evaluating the association of intratumoral activated fibroblast density detected by immunohistochemical (IHC) method and overall survival (OS) and/or disease-free survival (DFS) in breast cancer patients, then computed extracted data into hazard ratios (HRs) for OS, DFS and clinicopathological features such as lymph node metastasis, TNM stage with STATA 12...
2018: Journal of Cancer
Siyang Wen, Yixuan Hou, Lixin Fu, Lei Xi, Dan Yang, Maojia Zhao, Yilu Qin, Kexin Sun, Yong Teng, Manran Liu
Metastasis is the leading cause of breast cancer-related deaths. Cancer-associated fibroblasts (CAFs), the predominant stromal cell type in the breast tumour microenvironment, may contribute to cancer progression through interaction with tumour cells. Nonetheless, little is known about the details of the underlying mechanism. Here we found that interaction of interleukin 32 (IL32) with integrin β3 (encoded by ITGB3; a member of the integrin family) mediating the cross-talk between CAFs and breast cancer cells plays a crucial role in CAF-induced breast tumour invasiveness...
October 27, 2018: Cancer Letters
Ferial Amira Slim, Geneviève Ouellette, Kaoutar Ennour-Idrissi, Simon Jacob, Caroline Diorio, Francine Durocher
Background: Inflammation is a major player in breast cancer (BC) progression. Allograft-inflammatory factor-1 (AIF1) is a crucial mediator in the inflammatory response. AIF1 reportedly plays a role in BC, but the mechanism remains to be elucidated. We identified two AIF1 isoforms, AIF1v1 and AIF1v3, which were differentially expressed between affected and unaffected sisters from families with high risk of BC with no deleterious BRCA1/BRCA2 mutations (BRCAX). We investigated potential functions of AIFv1/v3 in BC of varying severity and breast adipose tissue by evaluating their expression, and association with metabolic and clinical parameters of BC patients...
2018: Cancer Cell International
Tuba Korkmaz, Fatih Aygenli, Handan Emisoglu, Gozde Ozcelik, Asena Canturk, Secil Yilmaz, Nuri Ozturk
The circadian clock confers daily rhythmicity on many biochemical and physiological functions and its disruption is associated with increased risks of developing obesity, diabetes, heart disease and cancer. Although, there are studies on the role of Bmal1 in carcinogenesis using germline, conditional or tissue-specific knockouts, it is still not well understood how BMAL1 gene affects cancer-related biological events at the molecular level. We, therefore, took an in vitro approach to understand the contribution of BMAL1 in this molecular mechanism using human breast epithelial cell lines by knocking out BMAL1 gene with CRISPR technology...
October 30, 2018: Scientific Reports
Ali Masjedi, Vida Hashemi, Mohammad Hojjat-Farsangi, Ghasem Ghalamfarsa, Gholamreza Azizi, Mehdi Yousefi, Farhad Jadidi-Niaragh
Despite remarkable improvements in cancer treatment approaches, breast cancer is still the main cause of cancer-related death in women. Its principal cause is the resistance of the cancer cells against conventional anticancer therapeutics, mainly in advanced disease stages. It has been shown that chronic inflammation in the tumor microenvironment facilitates tumor growth and induces resistance toward chemo- and radiotherapy. Overexpression of interleukin-6 (IL-6) cytokine in the tumor microenvironment has been demonstrated in numerous tumors including breast cancer...
December 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
A Bera, X-M Leighton, H Pollard, M Srivastava
Tumor suppressor function of Annexin-A7 (ANXA7) was demonstrated by cancer-prone phenotype in Anxa7(+/-) mice and ANXA7 profiling in human cancers including prostate and breast. Consistent with its more evident in vivo tumor suppressor role in prostate cancer, wild-type(wt)-ANXA7 in vitro induced similar G2-arrests, but reduced survival more drastically in prostate cancer cells compared to breast cancer cells (DU145 versus MDA-MB-231 and -435). In all three hormone-resistant cancer cell lines, wt-ANXA7 abolished the expression of the oncogenic low-molecular weight (LMW) cyclin E which was for the first time encountered in prostate cancer cells...
2018: Trends in Cancer Research
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