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Breast Cancer Cancer associated Fibroblast

Lauren E Hillers, Joseph V D'Amato, Tamara Chamberlin, Gretchen Paderta, Lisa M Arendt
Obese women diagnosed with breast cancer have an increased risk for metastasis, and the underlying mechanisms are not well established. Within the mammary gland, adipose-derived stromal cells (ASCs) are heterogeneous cells with the capacity to differentiate into multiple mesenchymal lineages. To study the effects of obesity on ASCs, mice were fed a control diet (CD) or high-fat diet (HFD) to induce obesity, and ASCs were isolated from the mammary glands of lean and obese mice. We observed that obesity increased ASCs proliferation, decreased differentiation potential, and upregulated expression of α-smooth muscle actin, a marker of activated fibroblasts, compared to ASCs from lean mice...
October 11, 2018: Neoplasia: An International Journal for Oncology Research
Margherita Leonardi, Eluisa Perna, Serena Tronnolone, David Colecchia, Mario Chiariello
Macroautophagy/autophagy is one of the major responses to stress in eukaryotic cells and is implicated in several pathological conditions such as infections, neurodegenerative diseases and cancer. Interestingly, cancer cells take full advantage of autophagy both to support tumor growth in adverse microenvironments and to oppose damages induced by anti-neoplastic therapies. Importantly, different human oncogenes are able to modulate this survival mechanism to support the transformation process, ultimately leading to 'autophagy addiction'...
October 5, 2018: Autophagy
Viviana Cremasco, Jillian L Astarita, Angelo L Grauel, Shilpa Keerthivasan, Kenzie D MacIsaac, Matthew C Woodruff, Michael Wu, Lotte Spel, Stephen Santoro, Zohreh Amoozgar, Tyler Laszewski, Sara Cruz-Migoni, Konstantin Knoblich, Anne L Fletcher, Martin LaFleur, Kai W Wucherpfennig, Ellen Pure, Glenn Dranoff, Michael Carroll, Shannon J Turley
Cancer-associated fibroblasts (CAFs) are generally associated with poor clinical outcome. CAFs support tumor growth in a variety of ways and can suppress antitumor immunity and response to immunotherapy. However, a precise understanding of CAF contributions to tumor growth and therapeutic response is lacking. Discrepancies in this field of study may stem from heterogeneity in composition and function of fibroblasts in the tumor microenvironment. Furthermore, it remains unclear whether CAFs directly interact with and suppress T cells...
September 28, 2018: Cancer Immunology Research
Farzaneh Ghaderi, Simin Ahmadvand, Amin Ramezani, Mehdi Montazer, Abbas Ghaderi
Breast cancer is the most prevalent malignancy among women around the world such that more than 1,400,000 new cases are being diagnosed each year. Despite immense studies over many years on diagnosis and treatment of breast cancer, about 30% of treated patients will relapse and require subsequent therapy. By development of hybridoma technology, murine monoclonal antibodies (MAbs) against several human tumor-associated antigens have been produced and characterized in many laboratories. The purpose of these studies is to generate effective monoclonal antibodies that could be useful in tumor diagnosis and therapy...
September 19, 2018: Biochemical and Biophysical Research Communications
Laryn Steadman, Susan Crook
Fibromatoses are soft tissue tumors composed of fibroblasts which commonly appear in the muscular aponeurosis of the abdomen. Mammary fibromatoses occur in only 0.2% of breast neoplasms and have been reported in association with prior breast augmentation and Gardner's syndrome. Multiple imaging modalities have been used to characterize the appearance of breast fibromatosis; however, it remains a tissue diagnosis given the variability both within and across modalities. We present the case of a 25-year-old female with a history of palpable breast mass who was evaluated with ultrasound, diagnostic mammography, MRI, and CT...
December 2018: Radiology Case Reports
Sreelatha K Hemalatha, Satheesh Kumar Sengodan, Revathy Nadhan, Jithin Dev, Reshma R Sushama, Veena Somasundaram, Ratheeshkumar Thankappan, Arathi Rajan, Neetha Rajan Latha, Geetu Rose Varghese, Arun Peter Mathew, Thara Somanathan, Priya Srinivas
It is known that Cancer Associated Fibroblast (CAFs) from the primary tumor site can accompany cancer cells to a secondary site during the process of metastasis. We hypothesize that these CAFs could be transformed to an altered cell type, which can be called as Metastasis Associated Fibroblasts (MAF) in turn can support, and convoy cancer cells for metastasis. There are no published reports that have characterized and distinguished CAFs from MAF. It is well established that some of the cancer cells within the tumor mass accumulate novel mutations prior to metastasis...
September 17, 2018: Scientific Reports
Ji Hee Lee, Hye Min Kim, Ja Seung Koo
OBJECTIVE: The purpose of this study is to investigate the expression of cancer-associated fibroblast (CAF)-related proteins and their implication in ductal carcinoma in situ (DCIS). METHODS: We constructed a tissue microarray of 223 cases of DCIS and examined immunohistochemical staining for the 7 CAF-related proteins. We classified DCIS into luminal type, human epidermal growth factor receptor-2 (HER-2) type, and triple negative breast cancer (TNBC) according to the immunohistochemical results for estrogen receptor, progesterone receptor, and HER-2...
September 17, 2018: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
Marcela Haro, Sandra Orsulic
The tumor microenvironment is increasingly recognized as an active participant in tumor progression. A recent pan-cancer genomic profile analysis has revealed that gene signatures representing components of the tumor microenvironment are robust predictors of survival. A stromal gene signature representing fibroblasts and extracellular matrix components has been associated with good survival in diffuse large B-cell lymphoma (DLBCL). Paradoxically, a closely related gene signature has been shown to correlate with poor survival in carcinomas, including breast, ovarian, pancreatic, and colorectal cancer...
2018: Frontiers in Cell and Developmental Biology
Bizhu Chu, An He, Yeteng Tian, Wan He, Peizhong Chen, Jintao Hu, Ruilian Xu, Wenbin Zhou, Mingjie Zhang, Pengyuan Yang, Shawn S C Li, Ying Sun, Pengfei Li, Tony Hunter, Ruijun Tian
Phosphotyrosine (pTyr)-regulated protein complexes play critical roles in cancer signaling. The systematic characterization of these protein complexes in tumor samples remains a challenge due to their limited access and the transient nature of pTyr-mediated interactions. We developed a hybrid chemical proteomics approach, termed Photo-pTyr-scaffold, by engineering Src homology 2 (SH2) domains, which specifically bind pTyr proteins, with both trifunctional chemical probes and genetic mutations to overcome these challenges...
September 18, 2018: Proceedings of the National Academy of Sciences of the United States of America
Ines Barone, Valentina Vircillo, Cinzia Giordano, Luca Gelsomino, Balázs Győrffy, Roberta Tarallo, Antonio Rinaldi, Giuseppina Bruno, Antonella Caruso, Francesco Romeo, Daniela Bonofiglio, Sebastiano Andò, Stefania Catalano
Cancer-associated Fibroblasts (CAFs), the principal components of tumor microenvironment, play multiple role in breast cancer progression. We have previously shown an oncosuppressive role of the nuclear Farnesoid X Receptor (FXR) in mammary epithelial cancer cells, here we assessed whether FXR activation may affect CAF tumor-promoting features. We showed that FXR is expressed in human CAFs isolated from four patients and treatment with the selective FXR agonist GW4064 decreased CAF migration, stress-fiber formation and contractility...
September 1, 2018: Cancer Letters
E Kumcu, H Unverdi, E Kaymaz, O Oral, D Turkbey, S Hucmenoglu
INTRODUCTION: Breast cancer is still a serious health problem in 21st century and diagnosis, treatment and prognosis of this malignant disease are subject to many research. While cancer research has been focused on tumour cells primarily, recent studies showed that tumour stroma contribute to carcinogenesis as well as tumour cells. Especially fibroblasts adjacent to epithelial tumour cells are not ordinary fibroblasts and play the critical role. Studies showed that these cancer associated fibroblasts (CAFs) have different genetic profile and protein expression...
August 2018: Malaysian Journal of Pathology
Andrew C Nelson, Heather L Machado, Kathryn L Schwertfeger
Refinements in early detection, surgical and radiation therapy, and hormone receptor-targeted treatments have improved the survival rates for breast cancer patients. However, the ability to reliably identify which non-invasive lesions and localized tumors have the ability to progress and/or metastasize remains a major unmet need in the field. The current diagnostic and therapeutic strategies focus on intrinsic alterations within carcinoma cells that are closely associated with proliferation. However, substantial accumulating evidence has indicated that permissive changes in the stromal tissues surrounding the carcinoma play an integral role in breast cancer tumor initiation and progression...
August 31, 2018: Journal of Mammary Gland Biology and Neoplasia
Hoe Suk Kim, Minji Jung, Sul Ki Choi, Jisu Woo, Yin Ji Piao, Eun Hye Hwang, Hyelim Kim, Seung Ja Kim, Woo Kyung Moon
BACKGROUND: The function of preadipocytes in the progression of early stage breast cancer has not been fully elucidated at the molecular level. To delineate the role of preadipocytes in breast cancer progression, we investigated the cross-talk between human breast ductal carcinoma in situ (DCIS) cells and preadipocytes with both an in vitro culture and xenograft tumor model. METHODS: GFP or RFP was transduced into human DCIS cell line cells or preadipocytes using lentivirus...
August 22, 2018: Journal of Experimental & Clinical Cancer Research: CR
Ilya D Ionov, Nicholas P Gorev, Larissa A Roslavtseva, David D Frenkel
OBJECTIVE: Cetirizine (CET) and thalidomide (THA) have been previously found to influence angiogenesis. The present study aimed to assess the ability of these drugs to influence mammary carcinogenesis in rats. MATERIALS AND METHODS: Sixty Sprague-Dawley female rats, aged 8 weeks, received 15 mg of 7,12-dimethylbenz(a)anthracene (DMBA) intragastrically. CET and THA (1.0 and 3.0 mg/kg, respectively) were administered orally for 118 days after DMBA administration...
August 21, 2018: Anti-cancer Drugs
Qingyu Cui, Bixiao Wang, Kaifu Li, Haichen Sun, Tao Hai, Yan Zhang, Hua Kang
Chemotherapy is an important comprehensive treatment for breast cancer, which targets micro-environment of tumors as well as their characterisitcs. A previous microarray analysis revealed that matrix metalloproteinase (MMP)-1 was highly upregulated in carcinoma-associated fibroblasts (CAFs) prior to and following treatment with Taxotere under co-culture conditions. However, whether the chemotherapeutic effects of Taxotere were influenced by the changes in MMP-1 remained unclear. The purpose of the present study was to investigate the impact and mechanism of CAFs in regulating the efficacy of Taxotere on breast cancer cells...
September 2018: Oncology Letters
Ling-Jun Zhao, Paul M Loewenstein, Maurice Green
We recently reported that adenovirus E1A enhances MYC association with the NuA4/Tip60 histone acetyltransferase (HAT) complex to activate a panel of genes enriched for DNA replication and cell cycle. Genes from this panel are highly expressed in examined cancer cell lines when compared to normal fibroblasts. To further understand gene regulation in cancer by MYC and the NuA4 complex, we performed RNA-seq analysis of MD-MB231 breast cancer cells following knockdown of MYC or Tip60 - the HAT enzyme of the NuA4 complex...
March 2018: Genes & Cancer
Shira Bernard, Megan Myers, Wei Bin Fang, Brandon Zinda, Curtis Smart, Diana Lambert, An Zou, Fang Fan, Nikki Cheng
With improved screening methods, the numbers of abnormal breast lesions diagnosed in women have been increasing over time. However, it remains unclear whether these breast lesions will develop into invasive cancers. To more effectively predict the outcome of breast lesions and determine a more appropriate course of treatment, it is important to understand the underlying mechanisms that regulate progression of non-invasive lesions to invasive breast cancers. A hallmark of invasive breast cancers is the accumulation of fibroblasts...
August 9, 2018: Journal of Mammary Gland Biology and Neoplasia
Benjamin D Landry, Thomas Leete, Ryan Richards, Peter Cruz-Gordillo, Hannah R Schwartz, Megan E Honeywell, Gary Ren, Alyssa D Schwartz, Shelly R Peyton, Michael J Lee
Due to tumor heterogeneity, most believe that effective treatments should be tailored to the features of an individual tumor or tumor subclass. It is still unclear, however, what information should be considered for optimal disease stratification, and most prior work focuses on tumor genomics. Here, we focus on the tumor microenvironment. Using a large-scale coculture assay optimized to measure drug-induced cell death, we identify tumor-stroma interactions that modulate drug sensitivity. Our data show that the chemo-insensitivity typically associated with aggressive subtypes of breast cancer is not observed if these cells are grown in 2D or 3D monoculture, but is manifested when these cells are cocultured with stromal cells, such as fibroblasts...
August 6, 2018: Molecular Systems Biology
Xiangdong Zhao, Faliang Xu, Nestor P Dominguez, Yuanping Xiong, Zhongxun Xiong, Hong Peng, Chloe Shay, Yong Teng
Although genetic amplification and overexpression of the fibroblast growth factor 19 (FGF19) gene are found in human breast cancer, mechanisms that contribute to such functional alterations remain elusive. We report here that high expression of FGF19 is associated with the aggressive malignant behavior and poor survival outcome of breast cancer patients. FGF19 is particularly highly expressed in luminal molecular subtype of breast tumors and its expression levels are positively associated with its secretion levels from breast cancer cells...
November 2018: Molecular Carcinogenesis
Tamara Muliaditan, Jonathan Caron, Mary Okesola, James W Opzoomer, Paris Kosti, Mirella Georgouli, Peter Gordon, Sharanpreet Lall, Desislava M Kuzeva, Luisa Pedro, Jacqueline D Shields, Cheryl E Gillett, Sandra S Diebold, Victoria Sanz-Moreno, Tony Ng, Esther Hoste, James N Arnold
Tumour-associated macrophages (TAMs) play an important role in tumour progression, which is facilitated by their ability to respond to environmental cues. Here we report, using murine models of breast cancer, that TAMs expressing fibroblast activation protein alpha (FAP) and haem oxygenase-1 (HO-1), which are also found in human breast cancer, represent a macrophage phenotype similar to that observed during the wound healing response. Importantly, the expression of a wound-like cytokine response within the tumour is clinically associated with poor prognosis in a variety of cancers...
July 27, 2018: Nature Communications
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