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premetastatic niche

Zhen Wang, Jun-Qiang Chen, Jin-Lu Liu, Lei Tian
Tumor microenvironment (TME) plays an integral part in the biology of cancer, participating in tumor initiation, progression, and response to therapy. Exosome is an important part of TME. Exosomes are small vesicles formed in vesicular bodies with a diameter of 30-100 nm and a classic "cup" or "dish" morphology. They can contain microRNAs, mRNAs, DNA fragments and proteins, which are shuttled from a donor cell to recipient cells. Exosomes secreted from tumor cells are called tumor-derived (TD) exosomes. There is emerging evidence that TD exosomes can construct a fertile environment to support tumor proliferation, angiogenesis, invasion and premetastatic niche preparation...
October 19, 2016: Journal of Translational Medicine
Jiang Jian, Yanli Pang, H Hannah Yan, Yongfen Min, Bhagelu R Achyut, M Christine Hollander, P Charles Lin, Xinhua Liang, Li Yang
Bone marrow-derived myeloid cells can form a premetastatic niche and provide a tumor-promoting microenvironment. However, subsets of myeloid cells have also been reported to have anti-tumor properties. It is not clear whether there is a transition between anti- and pro- tumor function of these myeloid cells, and if so, what are the underlying molecular mechanisms. Here we report platelet factor 4 (PF4), or CXCL4, but not the other family members CXCL9, 10, and 11, was produced at higher levels in the normal lung and early stage premetastatic lungs but decreased in later stage lungs...
May 19, 2016: Oncotarget
Nicholas Syn, Lingzhi Wang, Gautam Sethi, Jean-Paul Thiery, Boon-Cher Goh
Exosomes are extracellular signalosomes that facilitate eukaryotic intercellular communication under a wide range of normal physiological contexts. In malignancies, this regulatory circuit is co-opted to promote cancer cell survival and outgrowth. Tumour-derived exosomes (TDEs) carry a pro-EMT (epithelial-mesenchymal transition) programme including transforming growth factor beta (TGFβ), caveolin-1, hypoxia-inducible factor 1 alpha (HIF1α), and β-catenin that enhances the invasive and migratory capabilities of recipient cells, and contributes to stromal remodelling and premetastatic niche formation...
July 2016: Trends in Pharmacological Sciences
Pietro Parcesepe, Guido Giordano, Carmelo Laudanna, Antonio Febbraro, Massimo Pancione
Data from molecular profiles of tumors and tumor associated cells provide a model in which cancer cells can acquire the capability of avoiding immune surveillance by expressing an immune-like phenotype. Recent works reveal that expression of immune antigens (PDL1, CD47, CD73, CD14, CD68, MAC387, CD163, DAP12, and CD15) by tumor cells "immune resistance," combined with prometastatic function of nonmalignant infiltrating cells, may represent a strategy to overcome the rate-limiting steps of metastatic cascade through (a) enhanced interactions with protumorigenic myeloid cells and escape from T-dependent immune response mediated by CD8+ and natural killer (NK) cells; (b) production of immune mediators that establish a local and systemic tumor-supportive environment (premetastatic niche); (c) ability to survive either in the peripheral blood as circulating tumor cells (CTCs) or at the metastatic site forming a cooperative prometastatic loop with foreign "myeloid" cells, macrophages, and neutrophils, respectively...
2016: Gastroenterology Research and Practice
Jing Zhong, Yan Chen, Liang-Jing Wang
Lymphatic metastasis is commonly observed in gastric cancer (GC), but hematogenous metastasis is more likely responsible for the cancer-related mortality. Since Stephen Paget first introduced the "seed and soil hypothesis" a century ago, growing evidence recognizes that numerous essential secreted factors and signaling pathway effectors participate in the pre-metastatic niche formation and distant organ metastasis. The cross-talk between GC cells and surrounding microenvironment may consist of a series of interrelated steps, including epithelial mesenchymal transition, intravasation into blood vessels, circulating tumor cell translocation, and secondary organ metastasis...
February 28, 2016: World Journal of Gastroenterology: WJG
Ievgenia Pastushenko, Gert G Van den Eynden, Sandra Vicente-Arregui, Lucia Prieto-Torres, Ramiro Alvarez-Alegret, Ignacio Querol, Luc Y Dirix, Francisco J Carapeto, Peter B Vermeulen, Steven J Van Laere
Lymph node angio- and lymphangio-genesis have been shown to play an important role in the premetastatic niche of sentinel lymph nodes. In the current study we have investigated the association of angio- and lympangio-genesis related parameters in metastatic sentinel lymph nodes of patients with melanoma with the presence of nonsentinel and distant organ metastasis. Peritumoral and intratumoral relative blood and lymphatic vessel areas (evaluated by Chalkley method), blood and lymphatic microvessel densities, and the rates of blood and lymphatic vessel proliferation were assessed in primary tumors and sentinel lymph node metastasis of 44 patients with melanoma using CD34/Ki-67 and D240/Ki-67 immunohistochemical double staining...
May 2016: American Journal of Dermatopathology
Takaaki Masuda, Naoki Hayashi, Tomohiro Iguchi, Shuhei Ito, Hidetoshi Eguchi, Koshi Mimori
During the process of metastasis, which is the leading cause of cancer-related death, cancer cells dissociate from primary tumors, migrate to distal sites, and finally colonize, eventually leading to the formation of metastatic tumors. The migrating tumor cells in circulation, e.g., those found in peripheral blood (PB) or bone marrow (BM), are called circulating tumor cells (CTCs). CTCs in the BM are generally called disseminated tumor cells (DTCs). Many studies have reported the detection and characterization of CTCs to facilitate early diagnosis of relapse or metastasis and improve early detection and appropriate treatment decisions...
March 2016: Molecular Oncology
Wiktoria M Suchorska, Michal S Lach
Tumor cells have developed various mechanisms in defense against applied treatment, which prevent their total elimination from an organism. One of the underestimated mechanisms of defense is secretion of highly specialized double-membrane structures called exosomes. They play a crucial role in the control of the local microenvironment and intracellular communication. It has been shown that the exosomes can be carriers of various proteins, lipids, miRNAs and mRNAs. There are extensive data concerning the influence and participation by exosomes in metastasis and cancer progression...
March 2016: Oncology Reports
Catherine A Sánchez, Eliana I Andahur, Rodrigo Valenzuela, Enrique A Castellón, Juan A Fullá, Christian G Ramos, Juan C Triviño
The different prostate cancer (PCa) cell populations (bulk and cancer stem cells, CSCs) release exosomes that contain miRNAs that could modify the local or premetastatic niche. The analysis of the differential expression of miRNAs in exosomes allows evaluating the differential biological effect of both populations on the niche, and the identification of potential biomarkers and therapeutic targets. Five PCa primary cell cultures were established to originate bulk and CSCs cultures. From them, exosomes were purified by precipitation for miRNAs extraction to perform a comparative profile of miRNAs by next generation sequencing in an Illumina platform...
January 26, 2016: Oncotarget
Margot Zöller
Cancer diagnosis and therapy is steadily improving. Still, diagnosis is frequently late and diagnosis and follow-up procedures mostly are time-consuming and expensive. Searching for tumor-derived exosomes (TEX) in body fluids may provide an alternative, minimally invasive, yet highly reliable diagnostic tool. Beyond this, there is strong evidence that TEX could become a potent therapeutics. Exosomes, small vesicles delivered by many cells of the organism, are found in all body fluids. Exosomes are characterized by lipid composition, common and donor cell specific proteins, mRNA, small non-coding RNA including miRNA and DNA...
2016: Methods in Molecular Biology
Hangyi H Yan, Jian Jiang, Yanli Pang, B R Achyut, Michael Lizardo, Xinhua Liang, Kent Hunter, Chand Khanna, Christine Hollander, Li Yang
Tumor cell survival in the hostile distant organ is a rate-limiting step in cancer metastasis. Bone marrow-derived myeloid cells can form a premetastatic niche and provide a tumor-promoting microenvironment. However, it is unclear whether these myeloid cells in the premetastatic site have any direct effect on tumor cell survival. Here, we report that chemokine CCL9 was highly induced in Gr-1(+)CD11b(+) immature myeloid cells and in premetastatic lung in tumor-bearing mice. Knockdown of CCL9 in myeloid cells decreased tumor cell survival and metastasis...
December 15, 2015: Cancer Research
Sumanta Kumar Pal, Winston Vuong, Wang Zhang, Jiehui Deng, Xueli Liu, Courtney Carmichael, Nora Ruel, Manasvi Pinnamaneni, Przemyslaw Twardowski, Clayton Lau, Hua Yu, Robert A Figlin, Neeraj Agarwal, Jeremy O Jones
Preclinical studies have suggested that VEGFR1-positive cells potentially foster the development of metastases by establishing a "premetastatic niche." We sought to test this hypothesis in high-risk localized prostate cancer and assess potential niche modulation by the VEGFR1-targeting drug axitinib. Formalin-fixed, paraffin-embedded tissue derived from benign lymph nodes was collected and VEGFR1-positive cell clustering was assessed in benign lymph nodes via IHC. Recursive partitioning was used to define a threshold for VEGFR1 clustering that could segregate patients based on time to biochemical recurrence (TTBR)...
December 2015: Molecular Cancer Therapeutics
Henri H Versteeg
Blood coagulation is one of the most profound factors that influence cancer progression. Especially the initiator of coagulation, tissue factor (TF), has been subject to many studies investigating the overlap between coagulation and cancer. It has been known for decades that TF is a risk factor for metastasis, and in mouse models, TF drives metastasis in a coagulation-dependent manner. However, TF also serves as a cellular receptor to drive primary tumor growth and tumor angiogenesis. Nevertheless, recent studies have indicated that TF plays more fundamental roles in cancer biology...
October 2015: Seminars in Thrombosis and Hemostasis
Achim Krüger
The liver is recognized as the target organ of metastases of almost all prominent malignancies. Its unique biology renders this organ particularly susceptible to circulating disseminated tumour cells (DTCs), and it can be assumed that very early metastasis occurs in the liver. The premetastatic niche concept may explain very early metastasis, as it defines priming of a future target organ of metastasis by factors that may already be secreted from premalignant lesions. This review shows that comprehensive knowledge on mechanisms of premetastatic niche formation in the liver is based on pre-clinical models only and still rather rare, mostly due to the scarcity of mouse liver metastasis models displaying a tumour cell-free period in the liver or lack of liver-tropic syngeneic tumour cells to probe for the niche...
November 2015: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Meera Murgai, Amber Giles, Rosandra Kaplan
The primary tumor niche and the related but distinct premetastatic/metastatic niche comprise a number of essential players, including immune cells, stromal cells, and extracellular matrix. The cross-talk between these components is key to tumor progression. Many of these cell types and signaling pathways in the tumor microenvironment also are found in physiological and stem cell niches, such as the bone marrow, colonic crypt, and skin bulge. Here they play tightly regulated roles in wound healing and tissue homeostasis...
2015: Critical Reviews in Oncogenesis
Daniele Santini, Luciano Stumbo, Chiara Spoto, Loretta D'Onofrio, Francesco Pantano, Michele Iuliani, Marco Fioramonti, Alice Zoccoli, Giulia Ribelli, Vladimir Virzì, Bruno Vincenzi, Giuseppe Tonini
Bisphosphonates (BPs) are approved as standard therapy in breast cancer for the treatment of bone metastases, since they were demonstrated to reduce the prevalence of skeletal-related events including fractures and hypercalcemia. In the adjuvant setting, BPs can be given to prevent and treat tumor therapy-induced bone loss in premenopausal and postmenopausal women and, owing to their beneficial effect on bone turnover, have also been evaluated for prevention of bone metastases occurrence. In this article we will review the mechanisms through which BPs have been demonstrated to prevent premetastatic niche formation and cell proliferation in bone lesions...
2015: Breast Cancer Research: BCR
Daren Liu, Chao Li, Bogusz Trojanowicz, Xiaowen Li, Dike Shi, Chenni Zhan, Zhefang Wang, Li Chen
BACKGROUND: CD97 knockdown impairs the metastatic capacity of SGC-7901 gastric cancer cells. However, the role of CD97 in the distant lymphatic premetastatic niche formation of gastric cancer remains unknown. METHODS: Exosomes and the soluble fraction were isolated from SGC-L (an SGC-7901-cell-derived highly lymphatic metastatic cell line) and CD97-knockdown (SGC-L/CD97-kd) cells, and were co-cultured with gastric cancer cells. The metastatic capacity of the two cell lines was evaluated in vitro and in a footpad lymph node metastasis mouse model...
July 2016: Gastric Cancer
Alexandre de la Fuente, Lorena Alonso-Alconada, Clotilde Costa, Juan Cueva, Tomas Garcia-Caballero, Rafael Lopez-Lopez, Miguel Abal
BACKGROUND: Remodeling targeted tissues for reception of tumor cells metastasizing from primary lesions is a consequence of communication between the tumor and the environment that governs metastasis. This study describes a novel approach that aims to disrupt the process of metastasis by interfering with this intense dialogue. METHODS: Proteomics and adhesion assays identified exosomes purified from the ascitic fluid of ovarian cancer patients (n = 9) as intermediaries of tumor cell attachment...
September 2015: Journal of the National Cancer Institute
Weidong Ji, Yonghao Li, Yun He, Mingzhu Yin, Huanjiao Jenny Zhou, Titus J Boggon, Haifeng Zhang, Wang Min
Studies from tumor cells suggest that tumor-suppressor AIP1 inhibits epithelial-mesenchymal transition (EMT). However, the role of AIP1 in the tumor microenvironment has not been examined. We show that a global or vascular endothelial cell (EC)-specific deletion of the AIP1 gene in mice augments tumor growth and metastasis in melanoma and breast cancer models. AIP1-deficient vascular environment not only enhances tumor neovascularization and increases premetastatic niche formation, but also secretes tumor EMT-promoting factors...
September 1, 2015: Cancer Research
Andrew J Tompkins, Devasis Chatterjee, Michael Maddox, Justin Wang, Emily Arciero, Giovanni Camussi, Peter J Quesenberry, Joseph F Renzulli
Extracellular vesicles (EV) are small membrane-bound vesicles enriched in a selective repertoire of mRNA, miRNA, proteins and cell surface receptors from parental cells and are actively involved in the transmission of inter and intracellular signals. Cancer cells produce EV that contain cargo including DNA, mRNA, miRNA and proteins that allow EV to create epigenetic changes in target cells both locally and systemically. Cancer-derived EV play critical roles in tumorigenesis, cancer cell migration, metastasis, evasion of host immune defense, chemoresistance, and they promote a premetastatic niche favourable to micrometastatic seeding...
2015: Journal of Extracellular Vesicles
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