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https://www.readbyqxmd.com/read/28077297/exosomes-key-mediators-of-metastasis-and-pre-metastatic-niche-formation
#1
REVIEW
Richard J Lobb, Luize G Lima, Andreas Möller
While tumour cells are classically known to communicate via direct cell-to-cell contact and the secretion of soluble protein-based factors such as cytokines and growth factors, alternative novel mechanisms that promote tumour progression have recently emerged. Now, new critical components of the secretome thought to be involved in tumour progression are exosomes, small vesicles of endocytic origin that carry a variety of bioactive molecules, including proteins, lipids, RNA, as well as DNA molecules. Cancer cell-derived exosomes have been shown to participate in crucial steps of metastatic spread of a primary tumour, ranging from oncogenic reprogramming of malignant cells to formation of pre-metastatic niches...
January 8, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28075552/nanoparticles-coated-with-neutrophil-membranes-can-effectively-treat-cancer-metastasis
#2
Ting Kang, Qianqian Zhu, Dan Wei, Jingxian Feng, Jianhui Yao, Tianze Jiang, Qingxiang Song, Xunbin Wei, Hong-Zhuan Chen, Xiaoling Gao, Jun Chen
The dissemination, seeding and colonization of circulating tumor cells (CTC) serves as the root of distant metastasis. As a key step in the early stage of metastasis formation, colonization of CTC in the (pre-) metastatic niche appears to be a valuable target. Evidence showed that inflammatory neutrophils possess both CTC- and niche-targeting property by the intrinsic cell adhesion molecules on neutrophils. Inspired by this mechanism, we developed a nanosize neutrophil-mimicking drug delivery system (NM-NP) by coating neutrophils membranes on the surface of poly (latic-co-glycolic acid) nanoparticles (NP)...
January 11, 2017: ACS Nano
https://www.readbyqxmd.com/read/28012398/traditional-chinese-medicine-jianpi-bushen-therapy-suppresses-the-onset-of-pre-metastatic-niche-in-a-murine-model-of-spontaneous-lung-metastasis
#3
Xiaoyun Zhu, Yu Zhou, Qiu Xu, Jie Wu
BACKGROUND & AIM: Distinct metastasis accounts for the leading cause of mortality among patients with gastric cancer. The formation of pre-metastatic niche in the target organs provides permissive environments for the adhesion and subsequent growth of metastasized cancer cells. Targeting the pre-metastatic niche is a potential approach to prevent metastasis. Traditional Chinese medicine regimen called Jianpi Bushen therapy (JPBS) has been widely used in clinics to strengthen patients' abilities to fight cancer...
December 21, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27960084/extracellular-vesicles-in-cancer-cell-to-cell-mediators-of-metastasis
#4
REVIEW
Annette Becker, Basant Kumar Thakur, Joshua Mitchell Weiss, Han Sang Kim, Héctor Peinado, David Lyden
Tumor-secreted extracellular vesicles (EVs) are critical mediators of intercellular communication between tumor cells and stromal cells in local and distant microenvironments. Accordingly, EVs play an essential role in both primary tumor growth and metastatic evolution. EVs orchestrate multiple systemic pathophysiological processes, such as coagulation, vascular leakiness, and reprogramming of stromal recipient cells to support pre-metastatic niche formation and subsequent metastasis. Clinically, EVs may be biomarkers and novel therapeutic targets for cancer progression, particularly for predicting and preventing future metastatic development...
December 12, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27941674/biology-therapy-and-implications-of-tumor-exosomes-in-the-progression-of-melanoma
#5
REVIEW
Allison L Isola, Kevinn Eddy, Suzie Chen
Cancer is the second leading cause of death in the United States, and about 6% of the estimated cancer diagnoses this year will be melanoma cases. Melanomas are derived from transformation of the pigment producing cells of the skin, melanocytes. Early stage melanoma is usually curable by surgical resection, but late stage or subsequent secondary metastatic tumors are treated with some success with chemotherapies, radiation and/or immunotherapies. Most cancer patients die from metastatic disease, which is especially the case in melanoma...
December 9, 2016: Cancers
https://www.readbyqxmd.com/read/27846389/characteristics-and-significance-of-the-pre-metastatic-niche
#6
REVIEW
Yang Liu, Xuetao Cao
Primary tumors create a favorable microenvironment, namely, pre-metastatic niche, in secondary organs and tissue sites for subsequent metastases. The pre-metastatic niche can be primed and established through a complex interplay among primary tumor-derived factors, tumor-mobilized bone marrow-derived cells, and local stromal components. We review here our current understanding of the key components and underlying mechanisms for pre-metastatic niche formation. We propose six characteristics that define the pre-metastatic niche, which enable tumor cell colonization and promote metastasis, including immunosuppression, inflammation, angiogenesis/vascular permeability, lymphangiogenesis, organotropism, and reprogramming...
November 14, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27843540/radium-223-and-metastatic-castration-resistant-prostate-cancer-all-that-glitters-is-not-gold
#7
REVIEW
Carlo Aprile, Marco G Persico, Lorenzo Lodola, Federica E Buroni
After being approved by the National Drug Agency in several countries, Radium-223 (Ra-223) is gaining wide acceptance in the treatment of bone metastatic castration resistant prostate cancer. The exact mechanism of action remain unclear: The established model of direct alpha-particle irradiation from the remodelling bone surface, where Ra-223 accumulates, surrounding the tumor foci can explain a lethal effect only on metastatic microdeposits, but not on higher tumor burden. According to the "pre-metastatic niche model", it is likely that Ra-223 targets several non-tumoral cell types of the tumor microenvironment involved in the complex mechanism of cancer bone homing and colonization...
October 28, 2016: World Journal of Radiology
https://www.readbyqxmd.com/read/27823976/dysregulation-of-macrophage-polarization-is-associated-with-the-metastatic-process-in-osteosarcoma
#8
Clotilde Dumars, Jean-Michel Ngyuen, Aurélie Gaultier, Rachel Lanel, Nadège Corradini, François Gouin, Dominique Heymann, Marie-Françoise Heymann
Osteosarcoma (OS) is the most common bone sarcoma in adolescents, and has poor prognosis. A vicious cycle is established between OS cells and their microenvironment in order to facilitate the tumor growth and cell spreading. The present work aims to better characterize the tumor microenvironment in OS in order to identify new therapeutic targets relating to metastatic process. Tissue microarrays of pre-chemotherapy OS biopsies were used for characterizing the tumor niche by immunohistochemistry. Parameters studies included: immune cells (M1, M2-subtypes of tumor-associated macrophages (TAM); T, B lymphocytes; mast cells), vascularization (endothelial, perivascular cells), OPG, RANKL, and mitotic index...
November 13, 2016: Oncotarget
https://www.readbyqxmd.com/read/27797969/role-of-the-microenvironment-in-liver-metastasis-from-pre-to-prometastatic-niches
#9
REVIEW
Pnina Brodt
Liver metastases remain a major barrier to successful management of malignant disease, particularly for cancers of the gastrointestinal tract but also for other malignancies, such as breast carcinoma and melanoma. The ability of metastatic cells to survive and proliferate in the liver is determined by the outcome of complex, reciprocal interactions between tumor cells and different local resident subpopulations, including the sinusoidal endothelium, stellate, Kupffer, and inflammatory cells that are mediated through cell-cell and cell-extracellular matrix adhesion and the release of soluble factors...
December 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27785448/spotlight-on-talimogene-laherparepvec-for-the-treatment-of-melanoma-lesions-in-the-skin-and-lymph-nodes
#10
REVIEW
Marlana Orloff
On October 27, 2015, talimogene laherparepvec (T-VEC), a first in class intralesional oncolytic virotherapy, was granted the US Food and Drug Administration approval for the treatment of melanoma in the skin and lymph nodes. Its approval has added yet another therapeutic option to the growing list of effective therapies for melanoma. Though the Phase III OPTiM trial has demonstrated its efficacy as a single agent, the target patient population remains narrow. With numerous effective and tolerable treatments available for unresectable and metastatic melanoma, intralesional therapies such as T-VEC are still finding their niche...
2016: Oncolytic Virotherapy
https://www.readbyqxmd.com/read/27761367/the-role-of-micrornas-in-bone-metastasis
#11
Eugenio Zoni, Gabri van der Pluijm
The skeleton represents a common site of metastases for osteotropic cancers such as prostate and breast tumors and novel therapeutic targets and new markers for the monitoring of bone lesions are urgently needed. The formation of bone metastases is a complex process that starts at the level of the confined tumor and that is characterized by a dynamic crosstalk between the primary cancer and the future metastatic site, the bone. Factors released by the primary tumor contribute to prepare a fertile "soil", where a "pre-metastatic niche" is established prior to future colonization by cancer cells...
September 2016: Journal of Bone Oncology
https://www.readbyqxmd.com/read/27761366/the-role-of-lysyl-oxidase-the-extracellular-matrix-and-the-pre-metastatic-niche-in-bone-metastasis
#12
Alison Gartland, Janine T Erler, Thomas R Cox
Most deaths from solid cancers occur as a result of secondary metastasis to distant sites. Bone is the most frequent metastatic site for many cancer types and can account for up to 80% of cancer-related deaths in certain tumours. The progression from a discrete solid primary tumour to devastating and painful bone metastases is a complex process involving multiple cell types and steps. There is increasing evidence that modulation of the extracellular matrix plays an important role in the lethal transition from a primary to disseminated metastatic bone tumour...
September 2016: Journal of Bone Oncology
https://www.readbyqxmd.com/read/27602764/cytoskeleton-centric-protein-transportation-by-exosomes-transforms-tumor-favorable-macrophages
#13
Zhipeng Chen, Lijuan Yang, Yizhi Cui, Yanlong Zhou, Xingfeng Yin, Jiahui Guo, Gong Zhang, Tong Wang, Qing-Yu He
The exosome is a key initiator of pre-metastatic niche in numerous cancers, where macrophages serve as primary inducers of tumor microenvironment. However, the proteome that can be exosomally transported from cancer cells to macrophages has not been sufficiently characterized so far. Here, we used colorectal cancer (CRC) exosomes to educate tumor-favorable macrophages. With a SILAC-based mass spectrometry strategy, we successfully traced the proteome transported from CRC exosomes to macrophages. Such a proteome primarily focused on promoting cytoskeleton rearrangement, which was biologically validated with multiple cell lines...
October 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27593926/autophagy-in-cancer-metastasis
#14
E E Mowers, M N Sharifi, K F Macleod
Autophagy is a highly conserved self-degradative process that has a key role in cellular stress responses and survival. Recent work has begun to explore the function of autophagy in cancer metastasis, which is of particular interest given the dearth of effective therapeutic options for metastatic disease. Autophagy is induced upon progression of various human cancers to metastasis and together with data from genetically engineered mice and experimental metastasis models, a role for autophagy at nearly every phase of the metastatic cascade has been identified...
September 5, 2016: Oncogene
https://www.readbyqxmd.com/read/27506299/pancreatic-premalignant-lesions-secrete-tissue-inhibitor-of-metalloproteinases-1-which-activates-hepatic-stellate-cells-via%C3%A2-cd63-signaling-to-create-a-premetastatic-niche-in-the-liver
#15
Barbara Grünwald, Veronika Harant, Susanne Schaten, Monika Frühschütz, Ria Spallek, Bastian Höchst, Katharina Stutzer, Sonja Berchtold, Mert Erkan, Olga Prokopchuk, Marc Martignoni, Irene Esposito, Mathias Heikenwalder, Aayush Gupta, Jens Siveke, Paul Saftig, Percy Knolle, Dirk Wohlleber, Achim Krüger
BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDAC) metastasizes to liver at early stages, making this disease highly lethal. Tissue inhibitor of metalloproteinases-1 (TIMP1) creates a metastasis-susceptible environment in the liver. We investigated the role of TIMP1 and its receptor CD63 in metastasis of early-stage pancreatic tumors using mice and human cell lines and tissue samples. METHODS: We obtained liver and plasma samples from patients in Germany with chronic pancreatitis, pancreatic intra-epithelial neoplasia, or PDAC, as well as hepatic stellate cells (HSCs)...
November 2016: Gastroenterology
https://www.readbyqxmd.com/read/27505671/tumor-exosomal-rnas-promote-lung-pre-metastatic-niche-formation-by-activating-alveolar-epithelial-tlr3-to-recruit-neutrophils
#16
Yanfang Liu, Yan Gu, Yanmei Han, Qian Zhang, Zhengping Jiang, Xiang Zhang, Bo Huang, Xiaoqing Xu, Jianming Zheng, Xuetao Cao
The pre-metastatic niche educated by primary tumor-derived elements contributes to cancer metastasis. However, the role of host stromal cells in metastatic niche formation and organ-specific metastatic tropism is not clearly defined. Here, we demonstrate that lung epithelial cells are critical for initiating neutrophil recruitment and lung metastatic niche formation by sensing tumor exosomal RNAs via Toll-like receptor 3 (TLR3). TLR3-deficient mice show reduced lung metastasis in the spontaneous metastatic models...
August 8, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27505667/pre-metastatic-niche-formation-has-taken-its-toll
#17
Candia M Kenific, Laura Nogués, David Lyden
Pre-Metastatic Niches (PMNs) result from communications between primary tumors and the microenvironment of future distant metastasis via tumor-derived factors. In this issue of Cancer Cell, Liu et al. show that TLR3 activation in lung epithelial cells by tumor exosomal RNAs triggers neutrophil recruitment, which contributes to PMN formation and metastasis.
August 8, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27307317/the-endothelial-adrenomedullin-ramp2-system-regulates-vascular-integrity-and-suppresses-tumour-metastasis
#18
Megumu Tanaka, Teruhide Koyama, Takayuki Sakurai, Akiko Kamiyoshi, Yuka Ichikawa-Shindo, Hisaka Kawate, Tian Liu, Xian Xian, Akira Imai, Liuyu Zhai, Kazutaka Hirabayashi, Shinji Owa, Akihiro Yamauchi, Kyoko Igarashi, Shun'ichiro Taniguchi, Takayuki Shindo
AIMS: Controlling vascular integrity is expected to be a novel therapeutic target of cancers as well as cardiovascular diseases. Adrenomedullin (AM) and its receptor-modulating protein, RAMP2, have been identified as essential mediators of cardiovascular homeostasis. In this study, we used inducible vascular endothelial cell-specific RAMP2 knockout (DI-E-RAMP2(-/-)) mice to clarify the contribution made by the endogenous AM-RAMP2 system to angiogenesis and metastasis. METHODS AND RESULTS: Subcutaneously transplanted sarcoma or melanoma cells showed less growth and angiogenesis in DI-E-RAMP2(-/-) than in control mice...
September 2016: Cardiovascular Research
https://www.readbyqxmd.com/read/27272813/analysis-of-circulating-tumor-cells-in-prostate-cancer-patients-at-psa-recurrence-and-review-of-the-literature
#19
Salvatore Grisanti, Alessandro Antonelli, Michela Buglione, Camillo Almici, Chiara Foroni, Mario Sodano, Luca Triggiani, Diana Greco, Carlotta Palumbo, Mirella Marini, Stefano M Magrini, Alfredo Berruti, Claudio Simeone
BACKGROUND: Circulating tumor cells have been described in prostate cancer patients at diagnosis and in the metastatic phase but little is known on their role at biochemical PSA recurrence. PATIENTS AND METHODS: Patients radically cured with either prostatectomy or radiotherapy were sequentially included at PSA recurrence. The presence of CTCs was evaluated by the CellSearch system. RESULTS: Twenty-nine patients were accrued at PSA recurrence...
June 2016: Anticancer Research
https://www.readbyqxmd.com/read/27231155/autophagy-inhibition-delays-early-but-not-late-stage-metastatic-disease
#20
Rebecca A Barnard, Daniel P Regan, Ryan J Hansen, Paola Maycotte, Andrew Thorburn, Daniel L Gustafson
The autophagy pathway has been recognized as a mechanism of survival and therapy resistance in cancer, yet the extent of autophagy's function in metastatic progression is still unclear. Therefore, we used murine models of metastatic cancer to investigate the effect of autophagy modulation on metastasis development. Pharmacologic and genetic autophagy inhibition were able to impede cell proliferation in culture, but did not impact the development of experimentally induced 4T1 and B16-F10 metastases. Similarly, autophagy inhibition by adjuvant chloroquine (CQ) treatment did not delay metastasis in an orthotopic 4T1, tumor-resection model...
August 2016: Journal of Pharmacology and Experimental Therapeutics
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