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https://www.readbyqxmd.com/read/28424693/human-melanoma-derived-extracellular-vesicles-regulate-dendritic-cell-maturation
#1
Rachel L G Maus, James W Jakub, Wendy K Nevala, Trace A Christensen, Klara Noble-Orcutt, Zohar Sachs, Tina J Hieken, Svetomir N Markovic
Evolution of melanoma from a primary tumor to widespread metastasis is crucially dependent on lymphatic spread. The mechanisms regulating the initial step in metastatic dissemination via regional lymph nodes remain largely unknown; however, evidence supporting the establishment of a pre-metastatic niche is evolving. We have previously described a dysfunctional immune profile including reduced expression of dendritic cell (DC) maturation markers in the first node draining from the primary tumor, the sentinel lymph node (SLN)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28366542/key-biological-processes-driving-metastatic-spread-of-pancreatic-cancer-as-identified-by-multi-omics-studies
#2
REVIEW
T Y S Le Large, M F Bijlsma, G Kazemier, H M W van Laarhoven, E Giovannetti, C R Jimenez
Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy, characterized by a high metastatic burden, already at the time of diagnosis. The metastatic potential of PDAC is one of the main reasons for the poor outcome next to lack of significant improvement in effective treatments in the last decade. Key mutated driver genes, such as activating KRAS mutations, are concordantly expressed in primary and metastatic tumors. However, the biology behind the metastatic potential of PDAC is not fully understood...
March 30, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28347321/the-150-most-important-questions-in-cancer-research-and-clinical-oncology-series-questions-6-14-edited-by-chinese-journal-of-cancer
#3
EDITORIAL
(no author information available yet)
To accelerate our endeavors to overcome cancer, Chinese Journal of Cancer has launched a program of publishing 150 most important questions in cancer research and clinical oncology. In this article, nine more questions are presented as followed. Question 6. Why do nasopharyngeal carcinomas rarely metastasize to the brain? Question 7. Can distant spread of cancer cells be blocked by inhibiting the remodeling of high endothelial venules in the sentinel lymph node? Question 8. What sort of live-imaging techniques can be developed to directly observe the dynamic processes of metastasis? Question 9...
March 27, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/28344873/a-specific-immune-and-lymphatic-profile-characterizes-the-pre-metastatic-state-of-the-sentinel-lymph-node-in-patients-with-early-cervical-cancer
#4
Cédric Balsat, Silvia Blacher, Michael Herfs, Maureen Van de Velde, Nicolas Signolle, Philippe Sauthier, Charles Pottier, Stéphanie Gofflot, Marjolein De Cuypere, Philippe Delvenne, Frédéric Goffin, Agnès Noel, Frédéric Kridelka
The lymph node (LN) pre-metastatic niche is faintly characterized in lymphophilic human neoplasia, although LN metastasis is considered as the strongest prognostic marker of patient survival. Due to its specific dissemination through a complex bilateral pelvic lymphatic system, early cervical cancer is a relevant candidate for investigating the early nodal metastatic process. In the present study, we analyzed in-depth both the lymphatic vasculature and the immune climate of pre-metastatic sentinel LN (SLN), in 48 cases of FIGO stage IB1 cervical neoplasms...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28322342/therapy-targeted-to-the-metastatic-niche-is-effective-in-a-model-of-stage-iv-breast-cancer
#5
Byunghee Yoo, Amol Kavishwar, Ping Wang, Alana Ross, Pamela Pantazopoulos, Michael Dudley, Anna Moore, Zdravka Medarova
Treatment of stage IV metastatic breast cancer patients is limited to palliative options and represents an unmet clinical need. Here, we demonstrate that pharmacological inhibition of miRNA-10b - a master regulator of metastatic cell viability - leads to elimination of distant metastases in a mouse model of metastatic breast cancer. This was achieved using the miRNA-10b inhibitory nanodrug, MN-anti-miR10b, which consists of magnetic nanoparticles, conjugated to LNA-based miR-10b antagomirs. Intravenous injection of MN-anti-miR10b into mice bearing lung, bone, and brain metastases from breast cancer resulted in selective accumulation of the nanodrug in metastatic tumor cells...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28303905/pre-metastatic-niches-organ-specific-homes-for-metastases
#6
REVIEW
Héctor Peinado, Haiying Zhang, Irina R Matei, Bruno Costa-Silva, Ayuko Hoshino, Goncalo Rodrigues, Bethan Psaila, Rosandra N Kaplan, Jacqueline F Bromberg, Yibin Kang, Mina J Bissell, Thomas R Cox, Amato J Giaccia, Janine T Erler, Sachie Hiratsuka, Cyrus M Ghajar, David Lyden
It is well established that organs of future metastasis are not passive receivers of circulating tumour cells, but are instead selectively and actively modified by the primary tumour before metastatic spread has even occurred. Sowing the 'seeds' of metastasis requires the action of tumour-secreted factors and tumour-shed extracellular vesicles that enable the 'soil' at distant metastatic sites to encourage the outgrowth of incoming cancer cells. In this Review, we summarize the main processes and new mechanisms involved in the formation of the pre-metastatic niche...
March 17, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/28279189/therapeutic-strategies-of-drug-repositioning-targeting-autophagy-to-induce-cancer-cell-death-from-pathophysiology-to-treatment
#7
REVIEW
Go J Yoshida
The 2016 Nobel Prize in Physiology or Medicine was awarded to the researcher that discovered autophagy, which is an evolutionally conserved catabolic process which degrades cytoplasmic constituents and organelles in the lysosome. Autophagy plays a crucial role in both normal tissue homeostasis and tumor development and is necessary for cancer cells to adapt efficiently to an unfavorable tumor microenvironment characterized by hypo-nutrient conditions. This protein degradation process leads to amino acid recycling, which provides sufficient amino acid substrates for cellular survival and proliferation...
March 9, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28247413/mesothelial-to-mesenchymal-transition-as-a-possible-therapeutic-target-in-peritoneal-metastasis-of-ovarian-cancer
#8
Angela Rynne-Vidal, Chi Lam Au-Yeung, José A Jiménez-Heffernan, María Luisa Pérez-Lozano, Lucía Cremades-Jimeno, Carmen Bárcena, Ignacio Cristóbal-García, Concepción Fernández-Chacón, Tsz Lun Yeung, Samuel C Mok, Pilar Sandoval, Manuel López-Cabrera
Peritoneal dissemination is the primary metastatic route of ovarian cancer (OvCa), and is often accompanied by the accumulation of ascitic fluid. The peritoneal cavity is lined by mesothelial cells (MCs), which can be converted into carcinoma-associated fibroblasts (CAFs) through mesothelial-to-mesenchymal transition (MMT). Here, we demonstrate that MCs isolated from ascitic fluid (AFMCs) of OvCa patients with peritoneal implants also undergo MMT and promote subcutaneous tumour growth in mice. RNA sequencing of AFMCs revealed that MMT-related pathways - including transforming growth factor (TGF)-β signalling - are differentially regulated, and a gene signature was verified in peritoneal implants from OvCa patients...
March 1, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28238683/endothelial-notch1-activity-facilitates-metastasis
#9
Elfriede Wieland, Juan Rodriguez-Vita, Sven S Liebler, Carolin Mogler, Iris Moll, Stefanie E Herberich, Elisa Espinet, Esther Herpel, Amitai Menuchin, Jenny Chang-Claude, Michael Hoffmeister, Christoffer Gebhardt, Hermann Brenner, Andreas Trumpp, Christian W Siebel, Markus Hecker, Jochen Utikal, David Sprinzak, Andreas Fischer
Endothelial cells (ECs) provide angiocrine factors orchestrating tumor progression. Here, we show that activated Notch1 receptors (N1ICD) are frequently observed in ECs of human carcinomas and melanoma, and in ECs of the pre-metastatic niche in mice. EC N1ICD expression in melanoma correlated with shorter progression-free survival. Sustained N1ICD activity induced EC senescence, expression of chemokines and the adhesion molecule VCAM1. This promoted neutrophil infiltration, tumor cell (TC) adhesion to the endothelium, intravasation, lung colonization, and postsurgical metastasis...
February 12, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28186102/cancer-cell-secreted-igf2-instigates-fibroblasts-and-bone-marrow-derived-vascular-progenitor-cells-to-promote-cancer-progression
#10
Wen Wen Xu, Bin Li, Xin Yuan Guan, Sookja K Chung, Yang Wang, Yim Ling Yip, Simon Y K Law, Kin Tak Chan, Nikki P Y Lee, Kwok Wah Chan, Li Yan Xu, En Min Li, Sai Wah Tsao, Qing-Yu He, Annie L M Cheung
Local interactions between cancer cells and stroma can produce systemic effects on distant organs to govern cancer progression. Here we show that IGF2 secreted by inhibitor of differentiation (Id1)-overexpressing oesophageal cancer cells instigates VEGFR1-positive bone marrow cells in the tumour macroenvironment to form pre-metastatic niches at distant sites by increasing VEGF secretion from cancer-associated fibroblasts. Cancer cells are then attracted to the metastatic site via the CXCL5/CXCR2 axis. Bone marrow cells transplanted from nude mice bearing Id1-overexpressing oesophageal tumours enhance tumour growth and metastasis in recipient mice, whereas systemic administration of VEGFR1 antibody abrogates these effects...
February 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28151481/epigenetic-regulation-of-hgf-met-receptor-axis-is-critical-for-the-outgrowth-of-bone-metastasis-from-breast-carcinoma
#11
Paola Bendinelli, Paola Maroni, Emanuela Matteucci, Maria Alfonsina Desiderio
Our translational research deals with the influence of microenvironment on the phenotype and colonization of bone metastases from breast carcinoma, and on pre-metastatic niche formation. The aim of the present study was to clarify the origin of hepatocyte growth factor (HGF), ligand of Met receptor, the control of the axis HGF/Met by DNA methylation, and its importance for the nexus supportive cells-metastatic cells and for metastasis outgrowth. In bone metastasis of the 1833-xenograft model, DNA methyltransferase blockade using the chemotherapic drug 5-aza-2'-deoxycytidine (decitabine) strongly reduced the expression of HGF/Met receptor axis and of E-cadherin, with decrease of metastasis wideness and osteolysis, prolonging mice survival...
February 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28143493/the-yin-yan-of-ccl2-a-minor-role-in-neutrophil-anti-tumor-activity-in-vitro-but-a-major-role-on-the-outgrowth-of-metastatic-breast-cancer-lesions-in-the-lung-in-vivo
#12
Nicole Lavender, Jinming Yang, Sheau-Chiann Chen, Jiqing Sai, C Andrew Johnson, Philip Owens, Gregory D Ayers, Ann Richmond
BACKGROUND: The role of the chemokine CCL2 in breast cancer is controversial. While CCL2 recruits and activates pro-tumor macrophages, it is also reported to enhance neutrophil-mediated anti-tumor activity. Moreover, loss of CCL2 in early development enhances breast cancer progression. METHODS: To clarify these conflicting findings, we examined the ability of CCL2 to alter naïve and tumor entrained neutrophil production of ROS, release of granzyme-B, and killing of tumor cells in multiple mouse models of breast cancer...
January 31, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28137827/s100a9-induces-differentiation-of-acute-myeloid-leukemia-cells-through-tlr4
#13
Malika Laouedj, Mélanie R Tardif, Laurine Gil, Marie-Astrid Raquil, Asmaa Lachaab, Martin Pelletier, Philippe A Tessier, Frédéric Barabé
S100A8 and S100A9 are calcium-binding proteins predominantly expressed by neutrophils and monocytes, and play key roles in both normal and pathological inflammation. Recently, both proteins were found to promote tumor progression through the establishment of pre-metastatic niches and to inhibit antitumor immune responses. Although S100A8 and S100A9 have been studied in solid cancers, their functions in hematological malignancies remain poorly understood. However, S100A8 and S100A9 are highly expressed in acute myeloid leukemia (AML), and S100A8 expression has been linked to a poor prognosis in AML...
January 30, 2017: Blood
https://www.readbyqxmd.com/read/28135898/going-live-with-tumor-exosomes-and-microvesicles
#14
Vincent Hyenne, Olivier Lefebvre, Jacky G Goetz
Tumor extracellular vesicles (EVs), including exosomes, emerged as key drivers of the pro-tumorigenic dialog between the tumor mass and its microenvironment by mediating long and short distance communication. In vitro studies defined the capacity of tumor EVs to modify the phenotypes of stromal and tumor cells. These studies are now supported by a growing number of functional in vivo experiments. Remarkably, they allowed the identification of a new role for tumor EVs in priming the pre-metastatic niches (PMN)...
March 4, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/28128294/modeling-pre-metastatic-lymphvascular-niche-in-the-mouse-ear-sponge-assay
#15
Melissa García-Caballero, Maureen Van de Velde, Silvia Blacher, Vincent Lambert, Cédric Balsat, Charlotte Erpicum, Tania Durré, Frédéric Kridelka, Agnès Noel
Lymphangiogenesis, the formation of new lymphatic vessels, occurs in primary tumors and in draining lymph nodes leading to pre-metastatic niche formation. Reliable in vivo models are becoming instrumental for investigating alterations occurring in lymph nodes before tumor cell arrival. In this study, we demonstrate that B16F10 melanoma cell encapsulation in a biomaterial, and implantation in the mouse ear, prevents their rapid lymphatic spread observed when cells are directly injected in the ear. Vascular remodeling in lymph nodes was detected two weeks after sponge implantation, while their colonization by tumor cells occurred two weeks later...
January 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28077297/exosomes-key-mediators-of-metastasis-and-pre-metastatic-niche-formation
#16
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
#17
Ting Kang, Qianqian Zhu, Dan Wei, Jingxian Feng, Jianhui Yao, Tianze Jiang, Qingxiang Song, Xunbin Wei, Hongzhuan Chen, Xiaoling Gao, Jun Chen
The dissemination, seeding, and colonization of circulating tumor cells (CTCs) serve as the root of distant metastasis. As a key step in the early stage of metastasis formation, colonization of CTCs in the (pre-)metastatic niche appears to be a valuable target. Evidence showed that inflammatory neutrophils possess both a 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 (NPs)...
February 28, 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
#18
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...
February 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27960084/extracellular-vesicles-in-cancer-cell-to-cell-mediators-of-metastasis
#19
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
#20
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
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