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fibroblast cells metastasis

Eran Nizri, Shoshi Bar-David, Asaf Aizic, Neta Sternbach, Guy Lahat, Ido Wolf, Joseph Klausner
OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a peritumoral proliferation of fibroblasts and extracellular matrix production known as desmoplasia. We aimed to study desmoplasia in PDAC lymph node (LN) metastases. METHODS: We evaluated LNs from 66 patients with PDAC and LN metastases. We used immunohistochemistry and real-time polymerase chain reaction to phenotype the desmoplastic response. RESULTS: Desmoplasia was identified in 57% of patients with LN metastases (Des+)...
February 14, 2019: Pancreas
Satabdi Datta, Diptiman Choudhury, Amlan Das, Dipanwita Das Mukherjee, Moumita Dasgupta, Shreya Bandopadhyay, Gopal Chakrabarti
Paclitaxel is one of the most commonly used drugs for the treatment of nonsmall cell lung cancer (NSCLC). However acquired resistance to paclitaxel, epithelial to mesenchymal transition and cancer stem cell formation are the major obstacles for successful chemotherapy with this drug. Some of the major reasons behind chemoresistance development include increased ability of the cancer cells to survive under stress conditions by autophagy, increased expression of drug efflux pumps, tubulin mutations etc. In this study we found that inhibition of autophagy with chloroquine prevented development of paclitaxel resistance in A549 cells with time and potentiated the effect of paclitaxel by increased accumulation of superoxide-producing damaged mitochondria, with elevated ROS generation, it also increased the apoptotic rate and sub G0/ G1 phase arrest with time in A549 cells treated with paclitaxel and attenuated the metastatic potential and cancer stem cell population of the paclitaxel-resistant cells by ROS mediated modulation of the Wnt/β-catenin signaling pathway, thereby increasing paclitaxel sensitivity...
February 14, 2019: Apoptosis: An International Journal on Programmed Cell Death
Megan E Brasch, Giuseppe Passucci, Anushree C Gulvady, Christopher E Turner, M Lisa Manning, James H Henderson
Cell motility is critical to biological processes from wound healing to cancer metastasis to embryonic development. The involvement of organelles in cell motility is well established, but the role of organelle positional reorganization in cell motility remains poorly understood. Here we present an automated image analysis technique for tracking the shape and motion of Golgi bodies and cell nuclei. We quantify the relationship between nuclear orientation and the orientation of the Golgi body relative to the nucleus before, during, and after exposure of mouse fibroblasts to a controlled change in cell substrate topography, from flat to wrinkles, designed to trigger polarized motility...
2019: PloS One
Qiang Li Li, Yan-Ling Su, Min Zeng, Wei-Xi Shen
BACKGROUND: Human enabled homolog (ENAH; also known as human ortholog of mammalian enabled, hMENA) is a member of the enabled/vasodilator-stimulated phosphor protein family that regulates fibroblast movement and nervous system development. The ENAH over-expression promotes breast cancer (BC) cell invasion and metastasis. METHODS: We studied ENAH mRNA expression in various tumors and normal tissues using the ONCOMINE database, and in an array of cancer cell lines using Cancer Cell Line Encyclopedia data...
January 30, 2019: Clinical and Investigative Medicine. Médecine Clinique et Experimentale
Miguel Quintanilla, Lucía Montero-Montero, Jaime Renart, Ester Martín-Villar
Podoplanin is a small cell-surface mucin-like glycoprotein that plays a crucial role in the development of the alveoli, heart, and lymphatic vascular system. Emerging evidence indicates that it is also involved in the control of mammary stem-cell activity and biogenesis of platelets in the bone marrow, and exerts an important function in the immune response. Podoplanin expression is upregulated in different cell types, including fibroblasts, macrophages, T helper cells, and epithelial cells, during inflammation and cancer, where it plays important roles...
February 6, 2019: International Journal of Molecular Sciences
Fernanda G Kugeratski, Samuel J Atkinson, Lisa J Neilson, Sergio Lilla, John R P Knight, Jens Serneels, Amelie Juin, Shehab Ismail, David M Bryant, Elke K Markert, Laura M Machesky, Massimiliano Mazzone, Owen J Sansom, Sara Zanivan
Intratumoral hypoxia causes the formation of dysfunctional blood vessels, which contribute to tumor metastasis and reduce the efficacy of therapeutic treatments. Blood vessels are embedded in the tumor stroma of which cancer-associated fibroblasts (CAFs) constitute a prominent cellular component. We found that hypoxic human mammary CAFs promoted angiogenesis in CAF-endothelial cell cocultures in vitro. Mass spectrometry-based proteomic analysis of the CAF secretome unraveled that hypoxic CAFs contributed to blood vessel abnormalities by altering their secretion of various pro- and anti-angiogenic factors...
February 5, 2019: Science Signaling
J-J Song, W Li
OBJECTIVE: MicroRNA (miRNA) plays important roles in the progression of different cancers. In this study, we investigated the precise role of miR-10b in the growth and metastasis of colorectal cancer (CRC) cell. PATIENTS AND METHODS: The levels of miR-10b in CRC cell lines were detected using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) assay. A series of functional assays, including cell proliferation, colony formation, wound healing and transwell invasion were conducted using miR-10b transfected cells...
January 2019: European Review for Medical and Pharmacological Sciences
Zhuoshi Li, Tao Guo, Lei Fang, Nan Li, Xiaochao Wang, Peng Wang, Shilei Zhao, Fengzhou Li, Yanwei Cui, Xin Shu, Lei Zhao, Jinxiu Li, Chundong Gu
Carcinoma‑associated fibroblasts (CAFs) are essential for initiating lung cancer cell invasion and metastasis. An elevated MACC1 expression has been implicated in the progression of lung adenocarcinoma. Hitherto, the role of MACC1 in lung adenocarcinoma‑derived CAFs remains unclear. In this study, CAFs isolated from the tissues of patients with lung adenocarcinoma expressed typical CAF markers (shown by immunohistochemical and immunofluorescence analysis) and exhibited enhanced migration and invasion abilities when co‑cultured with A549 cells in a microfluidic model...
January 30, 2019: International Journal of Oncology
Jiangting Wang, Xiaowei Liu, Qin Zhuang, Rongrong Pan, Linlin Zou, Zhenbo Cen, Lijiang Tang
Cardiac fibrosis is closely associated with various heart diseases and is an important pathological feature of cardiac remodeling. However, detailed mechanisms underlying cardiac fibrosis remain largely unknown. Long noncoding RNAs (lncRNAs) are reported to serve significant roles in the development of cardiac fibrosis. The present study aimed to identify the role of a novel lncRNA, homeobox A11 antisense (HOXA11‑AS), in cardiac fibrosis. Overexpression of HOXA11‑AS in mouse cardiac fibroblasts (CFs) increased the expression of transforming growth factor β1 (TGFβ1) and its downstream molecules, while knockdown of HOXA11‑AS inhibited the TGFβ1 signaling pathway...
January 24, 2019: Molecular Medicine Reports
Brock A Humphries, Johanna M Buschhaus, Yu-Chih Chen, Henry R Haley, Tonela Qyli, Benjamin Chiang, Nathan Shen, Shrila Rajendran, Alyssa Cutter, Yu-Heng Cheng, Yu-Ting Chen, Jason Cong, Phillip C Spinosa, Euisik Yoon, Kathryn E Luker, Gary D Luker
Migration and invasion of cancer cells constitute fundamental processes in tumor progression and metastasis. Migratory cancer cells commonly upregulate expression of plasminogen activator inhibitor 1 (PAI1), and PAI1 correlates with poor prognosis in breast cancer. However, mechanisms by which PAI1 promotes migration of cancer cells remain incompletely defined. Here we show that increased PAI1 drives rearrangement of the actin cytoskeleton, mitochondrial fragmentation, and glycolytic metabolism in triple negative breast cancer (TNBC) cells...
February 4, 2019: Molecular Cancer Research: MCR
Noemi Eiro, Juan Francisco Carrión, Sandra Cid, Alejandro Andicoechea, José Luis García-Muñiz, Luis O González, Francisco J Vizoso
Current clinical-pathologic stratification factors do not allow clear identification of high-risk stage II colorectal cancer (CRC) patients. Therefore, the identification of additional prognostic markers is desirable. Toll-like receptor (TLR)-4 is activated during tumorigenesis and matrix metalloproteases (MMPs) are involved in invasion and metastasis. We aimed to evaluate the expression and clinical relevance of TLR4, MMP11 and MMP13 for patients with stage II CRC. Immunohistochemistry was used to study the expression of TLR4, MMP11 and MMP13 in 96 patients with stage II CRC...
February 1, 2019: Pathology Oncology Research: POR
Qinglei Gao, Zongyuan Yang, Sen Xu, Xiaoting Li, Xin Yang, Ping Jin, Yi Liu, Xiaoshui Zhou, Taoran Zhang, Cheng Gong, Xiao Wei, Dan Liu, Chaoyang Sun, Gang Chen, Junbo Hu, Li Meng, Jianfeng Zhou, Kenjiro Sawada, Robert Fruscio, Thomas W Grunt, Jörg Wischhusen, Víctor Manuel Vargas-Hernández, Bhavana Pothuri, Robert L Coleman
High-grade serous ovarian cancer (HGSOC) is hallmarked by early onset of peritoneal dissemination, which distinguishes it from low-grade serous ovarian cancer (LGSOC). Here, we describe the aggressive nature of HGSOC ascitic tumor cells (ATCs) characterized by integrin α5high (ITGA5high ) ATCs, which are prone to forming heterotypic spheroids with fibroblasts. We term these aggregates as metastatic units (MUs) in HGSOC for their advantageous metastatic capacity and active involvement in early peritoneal dissemination...
February 1, 2019: Journal of Experimental Medicine
Brian J DuChez, Andrew D Doyle, Emilios K Dimitriadis, Kenneth M Yamada
Durotaxis is a type of directed cell migration in which cells respond to a gradient of extracellular stiffness. Using automated tracking of positional data for large sample sizes of single migrating cells, we investigated 1) whether cancer cells can undergo durotaxis; 2) whether cell durotactic efficiency varies depending on the regional compliance of stiffness gradients; 3) whether a specific cell migration parameter such as speed or time of migration correlates with durotaxis; and 4) whether Arp2/3, previously implicated in leading edge dynamics and migration, contributes to cancer cell durotaxis...
January 12, 2019: Biophysical Journal
Jiefu Jin, Balaji Krishnamachary, James Dion Barnett, Samit Chatterjee, Di Chang, Yelena Mironchik, Flonne Wildes, Elizabeth Jaffee, Sridhar Nimmagadda, Zaver M Bhujwalla
Biomimetic nanoparticles (NPs) combine the flexibility and reproducibility of synthetic materials with the functionality of biological materials. Here, we developed and characterized biomimetic poly (lactic-co-glycolic acid) (PLGA) NPs coated with human cancer cell membrane fractions (CCMFs) to form CCMF coated PLGA (CCMF-PLGA) NPs. We evaluated the ability of these CCMF-PLGA NPs to disrupt cancer cell-stromal cell interactions, and to induce an immune response. Western blot analysis verified the plasma membrane purity of CCMFs...
February 1, 2019: ACS Applied Materials & Interfaces
Ben Yi Tew, Christophe Legendre, Gerald C Gooden, Kyle N Johnson, Rae Anne Martinez, Jeff Kiefer, Mark Bernstein, Jennifer Glen, Loren Butry, Aleksander Hinek, Steven A Toms, Bodour Salhia
The functional role of human derived stromal cells in the tumor microenviornment of CNS metastases (CM) remain understudied. The purpose of the current study was to isolate and characterize stromal cells of the tumor microenvironment in CM. Four different patient-derived cell lines (PDCs) of stromal and one PDC of tumorigenic origin were generated from breast or lung CM. PDCs were analyzed by DNA/RNA sequencing, DNA methylation profiling, and immunophenotypic assays. The stromal derived PDCs were termed CNS metastasis-associated stromal cells (cMASCs)...
January 30, 2019: Oncogene
Barbara Walch-Rückheim, Russalina Ströder, Laura Theobald, Jennifer Pahne-Zeppenfeld, Subramanya Hegde, Yoo-Jin Kim, Rainer Maria Bohle, Ingolf Juhasz-Böss, Erich-Franz Solomayer, Sigrun Smola
Persistent infection with high-risk human papillomavirus (HPV) is a prerequisite for the development of cervical cancer. HPV-transformed cells actively instruct their microenvironment, promoting chronic inflammation and cancer progression. We previously demonstrated that cervical cancer cells contribute to T-helper-17 (Th17) cell recruitment, a cell type with pro-tumorigenic properties. In this study we analysed the expression of the Th17-promoting cytokine Interleukin(IL)-23 in the cervical cancer micromilieu and found CD83+ mature dendritic cells (mDC) co-expressing IL-23 in the stroma of cervical squamous cell carcinomas in situ...
January 29, 2019: Cancer Research
Rei Mizuno, Kenji Kawada, Yoshiro Itatani, Ryotaro Ogawa, Yoshiyuki Kiyasu, Yoshiharu Sakai
Colorectal cancer (CRC) is one of the most common causes of cancer deaths worldwide and the number of CRC patients is increasing progressively. Despite the improvement of the surgical techniques and chemotherapy, we have not completely overcome this disease yet due to the metastases. Therefore, understanding the mechanisms through which metastasis occurs is important for overcoming CRC. Normal host cells in the tumor microenvironment, such as macrophages and fibroblasts, have been reported to promote the growth of CRCs...
January 27, 2019: International Journal of Molecular Sciences
Nobuhide Higashino, Yu-Ichiro Koma, Masayoshi Hosono, Nobuhisa Takase, Maiko Okamoto, Himiko Kodaira, Mari Nishio, Manabu Shigeoka, Yoshihiro Kakeji, Hiroshi Yokozaki
Esophageal squamous cell carcinoma (ESCC) is a highly aggressive tumor with frequent recurrence even after curative resection. The tumor microenvironment, which consists of non-cancer cells, such as cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs), was recently reported to promote several cancers, including ESCC. However, the role of CAF as a coordinator for tumor progression in ESCC remains to be elucidated. In our immunohistochemical investigation of ESCC tissues, we observed that the intensity of expression of two CAF markers-alpha smooth muscle actin (αSMA) and fibroblast activation protein (FAP)-in the tumor stroma was significantly correlated with the depth of tumor invasion, lymph node metastasis, advanced pathological stage, and poor prognosis...
January 25, 2019: Laboratory Investigation; a Journal of Technical Methods and Pathology
Jing Sun, Dan Yang, Shi-He Cui, Hai-Tao Zhang, Yu Fu, Jian-Cheng Wang, Qiang Zhang
Gemcitabine (Gem) as an anti-cancer agent has been limited by its short circulation time and rapid metabolism that reflects in low tumor uptake and low therapeutic efficiency. To improve its anti-tumor activity, a novel FAPα enzyme-activated prodrug of Z-GP-Gem modified at 4-amino group of Gem was developed, which could effectively release parent Gem based on the specific cleavage via FAPα enzyme-activation in tumor microenvironment. Compared to Gem, the Z-GP-Gem prodrug exhibited significantly enhanced inhibition of both tumor growth and pulmonary metastasis in BALB/c mice bearing orthotopic breast 4T1 tumors...
January 21, 2019: International Journal of Pharmaceutics
Corinna J Mohr, Friederike A Steudel, Dominic Gross, Peter Ruth, Wing-Yee Lo, Reiner Hoppe, Werner Schroth, Hiltrud Brauch, Stephan M Huber, Robert Lukowski
Several tumor entities have been reported to overexpress KCa 3.1 potassium channels due to epigenetic, transcriptional, or post-translational modifications. By modulating membrane potential, cell volume, or Ca2+ signaling, KCa 3.1 has been proposed to exert pivotal oncogenic functions in tumorigenesis, malignant progression, metastasis, and therapy resistance. Moreover, KCa 3.1 is expressed by tumor-promoting stroma cells such as fibroblasts and the tumor vasculature suggesting a role of KCa 3.1 in the adaptation of the tumor microenvironment...
January 17, 2019: Cancers
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