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https://www.readbyqxmd.com/read/28615370/molecular-pathways-targeting-the-microenvironment-of-liver-metastases
#1
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
#2
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
#3
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
https://www.readbyqxmd.com/read/28549790/the-inhibitor-of-differentiation-1-id1-enables-lung-cancer-liver-colonization-through-activation-of-an-emt-program-in-tumor-cells-and-establishment-of-the-pre-metastatic-niche
#4
Eduardo Castañón, Alex Soltermann, Inés López, Marta Román, Margarita Ecay, María Collantes, Miriam Redrado, Iosune Baraibar, José María López-Picazo, Christian Rolfo, Fernando Vidal-Vanaclocha, Luis Raez, Walter Weder, Alfonso Calvo, Ignacio Gil-Bazo
Id1 promotes carcinogenesis and metastasis, and predicts prognosis of non-small cell lung cancer (NSCLC)-adenocarcionoma patients. We hypothesized that Id1 may play a critical role in lung cancer colonization of the liver by affecting both tumor cells and the microenvironment. Depleted levels of Id1 in LLC (Lewis lung carcinoma cells, LLC shId1) significantly reduced cell proliferation and migration in vitro. Genetic loss of Id1 in the host tissue (Id1(-/-) mice) impaired liver colonization and increased survival of Id1(-/-) animals...
May 24, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28523150/cancer-s-smart-bombs-tumor-derived-exosomes-target-lung-epithelial-cells-triggering-pre-metastatic-niche-formation
#5
EDITORIAL
Dionysios Antonopoulos, Nikolaos A A Balatsos, Konstantinos I Gourgoulianis
No abstract text is available yet for this article.
April 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28499894/pathophysiology-of-bone-metastases-from-solid-malignancies
#6
Philippe Clézardin
Bone metastases are common complications of many cancers. Among the mechanisms that set the scene for the development of bone metastases, several are shared by all forms of metastatic dissemination (pre-metastatic niche formation and chemotactic attraction of malignant cells, which invade the host tissue) and others are specific of bone tissue (homing of malignant cells to bone marrow niches and acquisition of an osteomimetic cell phenotype). After a latency period that can last several years, the malignant cells can proliferate into tumors that alter the normal bone remodeling process by inducing dysregulation of osteoblast and osteoclast function...
May 9, 2017: Joint, Bone, Spine: Revue du Rhumatisme
https://www.readbyqxmd.com/read/28494752/mda-met-conditioned-medium-augments-the-chemoattractant-dependent-migration-of-mda-met-cells-towards-hfob-conditioned-medium-and-increases-collagenase-activity
#7
Karis Chin-Quee, Henry J Donahue
BACKGROUND: Metastasis of breast cancer displays site-specificity towards bone. Recently, studies have emerged indicating that primary tumors may remotely influence creation of a pre-metastatic niche. In this study, we used human fetal osteoblastic cells and MDA-MET, a metastatic and preferentially bone homing derivative of the breast cancer cell line MDA-MB-231. We examined 1) whether secreted factors from MDA-MET cells increase generation of chemoattractants by human foetal osteoblastic cells 2) whether MDA-MET cells were responsive to these chemoattractants and 3) the identity of these chemoattractants...
May 11, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28481877/cyp4a-in-tumor-associated-macrophages-promotes-pre-metastatic-niche-formation-and-metastasis
#8
X W Chen, T J Yu, J Zhang, Y Li, H L Chen, G F Yang, W Yu, Y Z Liu, X X Liu, C F Duan, H L Tang, M Qiu, C L Wang, H Zheng, J Yue, A M Guo, J Yang
Tumor-associated macrophages (TAMs) play an essential role in metastasis. However, what enables TAMs to have a superior capacity to establish pre-metastatic microenvironment in distant organs is unclear. Here we have begun to uncover the effects of cytochrome P450 (CYP) 4A in TAMs on lung pre-metastatic niche formation and metastasis. CYP4A(+) TAM infiltration was positively associated with metastasis, pre-metastatic niche formation and poor prognosis in breast cancer patients. The pharmacological inhibition of CYP4A reduced lung pre-metastatic niche formation (evidenced by a decrease in vascular endothelial growth factor receptor 1 positive (VEGFR1(+)) myeloid cell recruitment and pro-metastatic protein expression) and metastatic burden, accompanied with TAM polarization away from the M2 phenotype in spontaneous metastasis models of 4T1 breast cancer and B16F10 melanoma...
May 8, 2017: Oncogene
https://www.readbyqxmd.com/read/28455419/cxcl1-is-critical-for-pre-metastatic-niche-formation-and-metastasis-in-colorectal-cancer
#9
Dingzhi Wang, Haiyan Sun, Jie Wei, Bo Cen, Raymond N DuBois
Emerging evidence suggests that the primary tumor influences the development of supportive metastatic microenvironments, referred to as pre-metastatic niches, in certain distant organs before arrival of metastatic cells.  However, the mechanisms underlying the contributions of the primary tumor to pre-metastatic niche formation are not fully understood.  Here we demonstrate that colorectal carcinoma cells secrete VEGF-A, which stimulates tumor-associated macrophages to produce CXCL1 in the primary tumor.  Elevation of CXCL1 in pre-metastatic liver tissue recruited CXCR2-positive myeloid-derived suppressor cells (MDSC) to form a pre-metastatic niche that ultimately promoted liver metastases...
April 28, 2017: Cancer Research
https://www.readbyqxmd.com/read/28438662/never-let-it-go-stopping-key-mechanisms-underlying-metastasis-to-fight-pancreatic-cancer
#10
REVIEW
E Giovannetti, C L van der Borden, A E Frampton, A Ali, O Firuzi, G J Peters
Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive neoplasm, predicted to become the second leading cause of cancer-related deaths before 2030. This dismal trend is mainly due to lack of effective treatments against its metastatic behavior. Therefore, a better understanding of the key mechanisms underlying metastasis should provide new opportunities for therapeutic purposes. Genomic analyses revealed that aberrations that fuel PDAC tumorigenesis and progression, such as SMAD4 loss, are also implicated in metastasis...
April 21, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28424693/human-melanoma-derived-extracellular-vesicles-regulate-dendritic-cell-maturation
#11
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
#12
REVIEW
T Y S Le Large, M F Bijlsma, G Kazemier, H W M 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
#13
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
#14
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
#15
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
#16
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...
May 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
#17
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
#18
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...
June 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28238683/endothelial-notch1-activity-facilitates-metastasis
#19
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...
March 13, 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
#20
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
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