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https://www.readbyqxmd.com/read/28989814/engineering-the-pre-metastatic-niche
#1
Brian A Aguado, Grace G Bushnell, Shreyas S Rao, Jacqueline S Jeruss, Lonnie D Shea
The pre-metastatic niche - the accumulation of aberrant immune cells and extracellular matrix proteins in target organs - primes the initially healthy organ microenvironment and renders it amenable for subsequent metastatic cell colonization. By attracting metastatic cancer cells, mimics of the pre-metastatic niche offer both diagnostic and therapeutic potential. However, deconstructing the complexity of the niche by identifying the interactions between cell populations and the mediatory roles of the immune system, soluble factors, extracellular matrix proteins, and stromal cells has proved challenging...
2017: Nature biomedical engineering
https://www.readbyqxmd.com/read/28977990/exosomal-tetraspanins-mediate-cancer-metastasis-by-altering-host-microenvironment
#2
Jun Lu, Jun Li, Shuo Liu, Teng Wang, Alessandro Ianni, Eva Bober, Thomas Braun, Rong Xiang, Shijing Yue
The metastases of malignant tumors develop through a cascade of events. The establishment of a pre-metastatic micro-environment is initiated by communication between tumors and host. Exosomes come into focus as the most potent intercellular communicators playing a pivotal role in this process. Cancer cells release exosomes into the extracellular environment prior to metastasis. Tetraspanin is a type of 4 times transmembrane proteins. It may be involved in cell motility, adhesion, morphogenesis, as well as cell and vesicular membrane fusion...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28969005/pancreatic-cancer-derived-exosomes-promote-tumor-metastasis-and-liver-pre-metastatic-niche-formation
#3
Zeqian Yu, Susu Zhao, Long Ren, Lishan Wang, Zhangjun Chen, Robert M Hoffman, Jiahua Zhou
Exosomes play important roles in cell-cell communication, and are likely mediators of the metastatic cascade in cancer. This study examined the role of exosomes in pancreatic cancer cell adhesion, migration, and invasion. We isolated and purified exosomes from two isogenic pancreatic cancer cell lines with different metastatic potentials. Uptake of exosomes from highly metastatic Panc02-H7 cells decreased adhesion and increased migration and invasion capacity in weakly metastatic Panc02 cells in vitro. Exosomes from highly metastatic pancreatic cancer cells induced liver pre-metastatic niche formation in naïve mice and promoted primary tumor growth and liver metastasis in vivo...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28940209/chronic-psychological-stress-promotes-lung-metastatic-colonization-of-circulating-breast-cancer-cells-by-decorating-a-pre-metastatic-niche-through-activating-%C3%AE-adrenergic-signaling
#4
Hongyu Chen, Dan Liu, Liang Guo, Xiang Cheng, Ning Guo, Ming Shi
Numerous studies have indicated that primary tumors induce formation of a pre-metastatic niche in distant organs by secreting tumor-derived factors. The present study shows that pre-exposure to chronic stress enhanced lung colonization efficiency by circulating tumor cells, suggesting that chronic stress critically influences pre-metastatic lungs before arrival of disseminated tumor cells. Ablation of the sympathetic nerve function by 6-OHDA or blockage of the β-adrenergic signaling by propranolol remarkably suppressed stress-induced lung metastasis...
September 22, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28920957/klf4-dependent-perivascular-cell-plasticity-mediates-pre-metastatic-niche-formation-and-metastasis
#5
Meera Murgai, Wei Ju, Matthew Eason, Jessica Kline, Daniel W Beury, Sabina Kaczanowska, Markku M Miettinen, Michael Kruhlak, Haiyan Lei, Jack F Shern, Olga A Cherepanova, Gary K Owens, Rosandra N Kaplan
A deeper understanding of the metastatic process is required for the development of new therapies that improve patient survival. Metastatic tumor cell growth and survival in distant organs is facilitated by the formation of a pre-metastatic niche that is composed of hematopoietic cells, stromal cells and extracellular matrix (ECM). Perivascular cells, including vascular smooth muscle cells (vSMCs) and pericytes, are involved in new vessel formation and in promoting stem cell maintenance and proliferation. Given the well-described plasticity of perivascular cells, we hypothesized that perivascular cells similarly regulate tumor cell fate at metastatic sites...
October 2017: Nature Medicine
https://www.readbyqxmd.com/read/28884337/the-multifaceted-role-of-periostin-in-priming-the-tumor-microenvironments-for-tumor-progression
#6
REVIEW
Dan Cui, Zhengjie Huang, Yingfu Liu, Gaoliang Ouyang
Tumor microenvironment consists of tumor cells, stromal cells, extracellular matrix and a plethora of soluble components. The complex array of interactions between tumor cells and their surrounding tumor microenvironments contribute to the determination of the fate of tumor cells during tumorigenesis and metastasis. Matricellular protein periostin is generally absent in most adult tissues but is highly expressed in tumor microenvironments. Current evidence reveals that periostin plays a critical role in establishing and remodeling tumor microenvironments such as the metastatic niche, cancer stem cell niche, perivascular niche, pre-metastatic niche, fibrotic microenvironment and bone marrow microenvironment...
September 7, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28872058/nanoparticles-target-early-stage-breast-cancer-metastasis-in-vivo
#7
Evgeniya Goldman, Assaf Zinger, Dana da Silva, Zvi Yaari, Ashima Kajal, Dikla Vardi-Oknin, Mor Goldfeder, Josh E Schroeder, Janna Shainsky-Roitman, Dov Hershkovitz, Avi Schroeder
Despite advances in cancer therapy, treating cancer after it has metastasized remains an unmet clinical challenge. In this study we demonstrate that 100 nm liposomes target triple-negative murine breast-cancer metastases post intravenous administration. Metastatic breast cancer was induced in BALB/c mice either experimentally, by a tail vein injection of 4T1 cells, or spontaneously, after implanting a primary tumor xenograft. To track their biodistribution in vivo the liposomes were labeled with multi-modal diagnostic agents, including indocyanine green and rhodamine for whole-animal fluorescent imaging, gadolinium for magnetic resonance imaging (MRI), and europium for a quantitative biodistribution analysis...
September 5, 2017: Nanotechnology
https://www.readbyqxmd.com/read/28825725/s100a7-from-mechanism-to-cancer-therapy
#8
L Padilla, S Dakhel, J Adan, M Masa, J M Martinez, L Roque, T Coll, R Hervas, C Calvis, L Llinas, S Buenestado, J Castellsague, R Messeguer, F Mitjans, J L Hernandez
Within the tumor, malignant and stromal cells support each other by secreting a wide variety of growth factors and cytokines, allowing tumor growth and disease progression. The identification and regulation of those key factors in this crosstalk has opened the opportunity to develop new therapeutic strategies that not only act on the tumor cells but also on the stroma. Among these factors, S100A7 protein has gained interest in the last years. With key roles in cell motility its expression correlates with increased tumor growth, angiogenesis and metastatic potential...
August 21, 2017: Oncogene
https://www.readbyqxmd.com/read/28819453/s100-spect-uncovers-cellular-and-molecular-events-of-pre-metastatic-niche-formation-and-following-organ-specific-cancer-metastasis
#9
EDITORIAL
Masakiyo Sakaguchi
Great progress has been made in in vivo imaging for cancer metastasis. Eisenblaetter et al. developed an innovative S100A8/A9-specific single photon emission computed tomography (SPECT) probe for imaging and succeeded in detecting the metastatic organ favored by the cancer before the cancer arrival. By utilizing this advanced method, researchers have also found that cancer-derived monocytes are the main source of the abundant production of S100A8/A9 in the pre-metastatic area. The CCL2-CCR2 axis is associated with S100A8/A9 production...
2017: Theranostics
https://www.readbyqxmd.com/read/28796150/the-role-of-cancer-derived-exosomes-in-tumorigenicity-epithelial-to-mesenchymal-transition
#10
REVIEW
Robert H Blackwell, Kimberly E Foreman, Gopal N Gupta
Epithelial-to-mesenchymal transition (EMT) is a process by which epithelial cells lose their basement membrane interaction and acquire a more migratory, mesenchymal phenotype. EMT has been implicated in cancer cell progression, as cells transform and increase motility and invasiveness, induce angiogenesis, and metastasize. Exosomes are 30-100 nm membrane-bound vesicles that are formed and excreted by all cell types and released into the extracellular environment. Exosomal contents include DNA, mRNA, miRNA, as well as transmembrane- and membrane-bound proteins derived from their host cell contents...
August 10, 2017: Cancers
https://www.readbyqxmd.com/read/28744322/visualization-of-tumor-immune-interaction-target-specific-imaging-of-s100a8-a9-reveals-pre-metastatic-niche-establishment
#11
Michel Eisenblaetter, Fabian Flores-Borja, Jae Jin Lee, Christina Wefers, Hannah Smith, Rebekka Hueting, Margaret S Cooper, Philip J Blower, Dominic Patel, Manuel Rodriguez-Justo, Hanna Milewicz, Thomas Vogl, Johannes Roth, Andrew Tutt, Tobias Schaeffter, Tony Ng
Background Systemic cancer spread is preceded by the establishment of a permissive microenvironment in the target tissue of metastasis - the premetastatic niche. As crucial players in establishment of the pre-metastatic niche, myeloid derived suppressor cells (MDSC) release S100A8/A9, an exosomal protein that contributes to metastasis, angiogenesis, and immune suppression. We report the application of antibody-based single-photon emission computed tomography (SPECT) for detection of S100A8/A9 in vivo as an imaging marker for pre-metastatic tissue priming...
2017: Theranostics
https://www.readbyqxmd.com/read/28733553/exosomal-tetraspanins-mediate-cancer-metastasis-by-altering-host-microenvironment
#12
Jun Lu, Jun Li, Shuo Liu, Teng Wang, Alessandro Ianni, Eva Bober, Thomas Braun, Rong Xiang, Shijing Yue
The metastases of malignant tumors develop through a cascade of events. The establishment of a pre-metastatic micro-environment is initiated by communication between tumors and host. Exosomes come into focus as the most potent intercellular communicators playing a pivotal role in this process. Cancer cells release exosomes into the extracellular environment prior to metastasis. Tetraspanin is a type of 4 times transmembrane proteins. It may be involved in cell motility, adhesion, morphogenesis, as well as cell and vesicular membrane fusion...
July 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28725292/-pre-metastatic-niches-in-breast-cancer-are-they-created-by-or-prior-to-the-tumour-onset-flammer-syndrome-relevance-to-address-the-question
#13
Rostyslav Bubnov, Jiri Polivka, Pavol Zubor, Katarzyna Konieczka, Olga Golubnitschaja
Breast cancer (BC) epidemic in the twenty-first century is characterised by around half a million deaths and 1.7 million new cases registered annually worldwide. Metastatic disease is the major cause of death in BC patient cohorts. Current statistics are much alarming from the viewpoint of the early mortality amongst BC patients with de novo metastatic disease. A new paradigm of so-called "pre-metastatic niches" may sufficiently promote our knowledge regarding potential pathomechanisms, individual predisposition and prognosis in development and progression of the metastatic disease...
June 2017: EPMA Journal
https://www.readbyqxmd.com/read/28720577/lysyl-oxidase-like-protein-loxl2-promotes-lung-metastasis-of-breast-cancer
#14
Fernando Salvador, Alberto Martin, Celia López-Menéndez, Gema Moreno-Bueno, Vanesa Santos, Alberto Vazquez-Naharro, Patricia G Santamaría, Saleta Morales, Pierre Dubus, Laura Muinelo-Romay, Rafael López López, Jason C Tung, Valerie M Weaver, Francisco Portillo, Amparo Cano
The lysyl oxidase-like protein LOXL2 has been suggested to contribute to tumor progression and metastasis, but in vivo evidence has been lacking. Here we provide functional evidence that LOXL2 is a key driver of breast cancer metastasis in two conditional transgenic mouse models of PyMT-induced breast cancer. LOXL2 ablation in mammary tumor cells dramatically decreased lung metastasis, whereas LOXL2 overexpression promoted metastatic tumor growth. LOXL2 depletion or overexpression in tumor cells does not affect extracellular matrix stiffness or organization in primary and metastatic tumors, implying a function for LOXL2 independent of its conventional role in extracellular matrix remodeling...
July 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28711943/pancreatic-cancer-derived-exosomes-promote-tumor-metastasis-and-liver-pre-metastatic-niche-formation
#15
Zeqian Yu, Susu Zhao, Long Ren, Lishan Wang, Zhangjun Chen, Robert M Hoffman, Jiahua Zhou
Exosomes play important roles in cell-cell communication, and are likely mediators of the metastatic cascade in cancer. This study examined the role of exosomes in pancreatic cancer cell adhesion, migration, and invasion. We isolated and purified exosomes from two isogenic pancreatic cancer cell lines with different metastatic potentials. Uptake of exosomes from highly metastatic Panc02-H7 cells decreased adhesion and increased migration and invasion capacity in weakly metastatic Panc02 cells in vitro. Exosomes from highly metastatic pancreatic cancer cells induced liver pre-metastatic niche formation in naïve mice and promoted primary tumor growth and liver metastasis in vivo...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28706128/transcriptome-analysis-reveals-a-role-for-the-endothelial-anp-gc-a-signaling-in-interfering-with-pre-metastatic-niche-formation-by-solid-cancers
#16
Takashi Nojiri, Miki Arai, Yutaka Suzuki, Motofumi Kumazoe, Takeshi Tokudome, Koichi Miura, Jun Hino, Hiroshi Hosoda, Mikiya Miyazato, Meinoshin Okumura, Shinpei Kawaoka, Kenji Kangawa
Cancer establishes a microenvironment called the pre-metastatic niche in distant organs where disseminated cancer cells can efficiently metastasize. Pre-metastatic niche formation requires various genetic factors. Previous studies suggest that inhibiting a single niche-factor is insufficient to completely block pre-metastatic niche formation especially in human patients. Here we show that the atrial natriuretic peptide (ANP), an endogenous hormone produced by the heart, inhibits pre-metastatic niche formation and metastasis of murine solid cancer models when pharmacologically supplied in vivo...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28658220/whole-body-imaging-of-lymphovascular-niches-identifies-pre-metastatic-roles-of-midkine
#17
David Olmeda, Daniela Cerezo-Wallis, Erica Riveiro-Falkenbach, Paula C Pennacchi, Marta Contreras-Alcalde, Nuria Ibarz, Metehan Cifdaloz, Xavier Catena, Tonantzin G Calvo, Estela Cañón, Direna Alonso-Curbelo, Javier Suarez, Lisa Osterloh, Osvaldo Graña, Francisca Mulero, Diego Megías, Marta Cañamero, Jorge L Martínez-Torrecuadrada, Chandrani Mondal, Julie Di Martino, David Lora, Inés Martinez-Corral, J Javier Bravo-Cordero, Javier Muñoz, Susana Puig, Pablo Ortiz-Romero, José L Rodriguez-Peralto, Sagrario Ortega, María S Soengas
Cutaneous melanoma is a type of cancer with an inherent potential for lymph node colonization, which is generally preceded by neolymphangiogenesis. However, sentinel lymph node removal does not necessarily extend the overall survival of patients with melanoma. Moreover, lymphatic vessels collapse and become dysfunctional as melanomas progress. Therefore, it is unclear whether (and how) lymphangiogenesis contributes to visceral metastasis. Soluble and vesicle-associated proteins secreted by tumours and/or their stroma have been proposed to condition pre-metastatic sites in patients with melanoma...
June 28, 2017: Nature
https://www.readbyqxmd.com/read/28615370/molecular-pathways-targeting-the-microenvironment-of-liver-metastases
#18
Simon Milette, Jason K Sicklick, Andrew M Lowy, Pnina Brodt
Curative treatment for metastatic solid cancers remains elusive. The liver, which is nourished by a rich blood supply from both the arterial and portal venous systems is the most common site of visceral metastases, particularly from cancers arising in the gastrointestinal (GI) tract, with colorectal cancer (CRC) being the predominant primary site in Western countries. A mounting body of evidence suggests that the liver microenvironment (LME) provides autocrine and paracrine signals originating from both parenchymal and non-parenchymal cells, that collectively create both pre-and pro-metastatic niches for the development of hepatic metastases...
June 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28600504/amphiregulin-contained-in-nsclc-exosomes-induces-osteoclast-differentiation-through-the-activation-of-egfr-pathway
#19
Simona Taverna, Marzia Pucci, Marco Giallombardo, Maria Antonietta Di Bella, Mariacarmela Santarpia, Pablo Reclusa, Ignacio Gil-Bazo, Christian Rolfo, Riccardo Alessandro
Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths worldwide. The majority of patients are diagnosed in advanced disease stage. Bone metastasis is the most frequent complication in NSCLC resulting in osteolytic lesions. The perfect balance between bone-resorbing osteoclasts and bone-forming osteoblasts activity is lost in bone metastasis, inducing osteoclastogenesis. In NSCLC, the epidermal growth factor receptor (EGFR) pathway is constitutively activated. EGFR binds Amphiregulin (AREG) that is overexpressed in several cancers such as colon, breast and lung...
June 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28576744/jak-stat-signaling-and-cancer-opportunities-benefits-and-side-effects-of-targeted-inhibition
#20
REVIEW
Bernd Groner, Viktoria von Manstein
The effects of Jak Stat signaling and the persistent activation of Stat3 and Stat5 on tumor cell survival, proliferation and invasion have made the Jak Stat pathway a favorite target for drug development and cancer therapy. This notion was strengthened when additional biological functions of Stat signaling in cancer and their roles in the regulation of cytokine dependent inflammation and immunity in the tumor microenvironment were discovered. Stats act not only as transcriptional inducers, but affect gene expression via epigenetic modifications, induce epithelial mesenchymal transition, generate a pro-tumorigenic microenvironment, promote cancer stem cell self-renewal and differentiation, and help to establish the pre-metastatic niche formation...
May 30, 2017: Molecular and Cellular Endocrinology
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