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https://www.readbyqxmd.com/read/28733553/exosomal-tetraspanins-mediate-cancer-metastasis-by-altering-host-microenvironment
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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-premetastatic-niche-formation-and-metastasis-in-colorectal-cancer
#15
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 premetastatic niches, in certain distant organs before arrival of metastatic cells. However, the mechanisms underlying the contributions of the primary tumor to premetastatic niche formation are not fully understood. Here, we demonstrate that colorectal carcinoma cells secrete VEGFA, which stimulates tumor-associated macrophages to produce CXCL1 in the primary tumor. Elevation of CXCL1 in premetastatic liver tissue recruited CXCR2-positive myeloid-derived suppressor cells (MDSC) to form a premetastatic niche that ultimately promoted liver metastases...
July 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28438662/never-let-it-go-stopping-key-mechanisms-underlying-metastasis-to-fight-pancreatic-cancer
#16
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 22, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28424693/human-melanoma-derived-extracellular-vesicles-regulate-dendritic-cell-maturation
#17
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
#18
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
#19
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
#20
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
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