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Prostate cancer bone microenvironment

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https://www.readbyqxmd.com/read/29212270/exosomal-mir-141-3p-regulates-osteoblast-activity-to-promote-the-osteoblastic-metastasis-of-prostate-cancer
#1
Yun Ye, Su-Liang Li, Yue-Yun Ma, Yan-Jun Diao, Liu Yang, Ming-Quan Su, Zhuo Li, Yang Ji, Juan Wang, Lin Lei, Wei-Xiao Fan, La-Xiu Li, Yi Xu, Xiao-Ke Hao
Exosomes from cancer cells, which contain microRNA and reach metastasis loci prior to cancer cells, stimulate the formation of a metastatic microenvironment. Previous studies have shown that exosomal miR-141-3p is associated with metastatic prostate cancer (PCa). However, the role and regulatory mechanism of miR-141-3p in the microenvironment of bone metastases require further study. In this study, we performed a series of experiments in vivo and in vitro to determine whether exosomal miR-141-3p from MDA PCa 2b cells regulates osteoblast activity to promote osteoblastic metastasis...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29152128/modulation-of-cabozantinib-efficacy-by-the-prostate-tumor-microenvironment
#2
Manisha Tripathi, Srinivas Nandana, Sandrine Billet, Karen A Cavassani, Rajeev Mishra, Leland W K Chung, Edwin M Posadas, Neil A Bhowmick
The tumor microenvironment (TME) is increasingly recognized as the arbiter of metastatic progression and drug resistance in advanced prostate cancer (PCa). Cabozantinib is a potent tyrosine kinase inhibitor (TKI) with reported biological activity in the PCa epithelia, but failed to provide an overall survival benefit in phase 3 clinical trials. However, the promising biologic efficacy of the drug in early trials warranted a better understanding of the mechanism of action, with the goal of improving patient selection for TKI-based therapy such as cabozantinib...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29101110/the-biology-of-bone-metastasis
#3
Mark Esposito, Theresa Guise, Yibin Kang
Bone metastasis, or the development of secondary tumors within the bone of cancer patients, is a debilitating and incurable disease. Despite its morbidity, the biology of bone metastasis represents one of the most complex and intriguing of all oncogenic processes. This complexity derives from the intricately organized bone microenvironment in which the various stages of hematopoiesis, osteogenesis, and osteolysis are jointly regulated but spatially restricted. Disseminated tumor cells (DTCs) from various common malignancies such as breast, prostate, lung, and kidney cancers or myeloma are uniquely primed to subvert these endogenous bone stromal elements to grow into pathological osteolytic or osteoblastic lesions...
November 3, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/29094177/bone-marrow-microenvironment-as-a-regulator-and-therapeutic-target-for-prostate-cancer-bone-metastasis
#4
REVIEW
Sun H Park, Evan T Keller, Yusuke Shiozawa
Bone is the most common site of prostate cancer metastasis. Once prostate cancer cells metastasize to bone, the mortality rate of prostate cancer patients increases significantly. Furthermore, bone metastases produce multiple skeletal complications, including bone pain that impairs the patients' quality of life. Effective therapies for bone metastatic disease are underdeveloped with most current therapies being primarily palliative with modest survival benefit. Although the exact mechanisms through which prostate cancer metastasizes to bone are unclear, growing evidence suggests that the bone marrow microenvironment, particularly its hematopoietic activity, is a significant mediator of prostate cancer bone tropism...
November 1, 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/29080972/the-proteasome-and-myeloma-associated-bone-disease
#5
REVIEW
Fabrizio Accardi, Denise Toscani, Federica Costa, Franco Aversa, Nicola Giuliani
Bone disease is the hallmark of multiple myeloma (MM), a hematological malignancy characterized by osteolytic lesions due to a severe uncoupled and unbalanced bone remodeling with pronounced osteoblast suppression. Bone metastasis is also a frequent complication of solid tumors including advanced breast or prostate cancer. In the past years, the ubiquitin-proteasome pathway has been proved critical in regulating the balance between bone formation and bone resorption. Proteasome inhibitors (PIs) are a new class of drugs, currently used in the treatment of MM, that affect both tumor cells and bone microenvironment...
October 28, 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/29030409/clinical-relevance-of-androgen-receptor-alterations-in-prostate-cancer
#6
REVIEW
Emma Jernberg, Anders Bergh, Pernilla Wikström
Prostate cancer (PC) remains a leading cause of cancer-related deaths among men worldwide, despite continuously improved treatment strategies. Patients with metastatic disease are treated by androgen deprivation therapy (ADT) that with time results in the development of castration-resistant prostate cancer (CRPC) usually established as metastases within bone tissue. The androgen receptor (AR) transcription factor is the main driver of CRPC development and of acquired resistance to drugs given for treatment of CRPC, while a minority of patients have CRPC that is non-AR driven...
November 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28981962/the-bmp-antagonist-noggin-is-produced-by-osteoblasts-in-response-to-the-presence-of-prostate-cancer-cells
#7
Huda F AlShaibi, Farid Ahmed, Clive Buckle, Ann Cm Fowles, Jalaluddin Awlia, Marco G Cecchini, Colby L Eaton
BACKGROUND: Bone metastasis is a key event responsible for morbidity in prostate cancer patients. Interactions between prostate cancer cells and the bone microenvironment facilitate survival of tumour cells and alter bone turnover, a process that is thought to enhance the growth of metastases in this site. This study aimed to test the hypothesis that the presence of tumours cells increases TGFβ signaling in bone and that this regulates the proliferation and differentiation of osteoblastic lineage cells in metastatic sites...
October 5, 2017: Biotechnology and Applied Biochemistry
https://www.readbyqxmd.com/read/28957694/endothelial-cells-as-precursors-for-osteoblasts-in-the-metastatic-prostate-cancer-bone
#8
Ana E Paiva, Luiza Lousado, Viviani M Almeida, Julia P Andreotti, Gabryella S P Santos, Patrick O Azevedo, Isadora F G Sena, Pedro H D M Prazeres, Isabella T Borges, Vasco Azevedo, Akiva Mintz, Alexander Birbrair
Prostate cancer cells metastasize to the bones, causing ectopic bone formation, which results in fractures and pain. The cellular mechanisms underlying new bone production are unknown. In a recent study, Lin and colleagues, by using state-of-the-art techniques, including prostate cancer mouse models in combination with sophisticated in vivo lineage-tracing technologies, revealed that endothelial cells form osteoblasts induced by prostate cancer metastasis in the bone. Strikingly, genetic deletion of osteorix protein from endothelial cells affected prostate cancer-induced osteogenesis in vivo...
November 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28919714/radium-223-dichloride-for-prostate-cancer-treatment
#9
REVIEW
Emmanuel Deshayes, Mathieu Roumiguie, Constance Thibault, Philippe Beuzeboc, Florent Cachin, Christophe Hennequin, Damien Huglo, François Rozet, Diana Kassab-Chahmi, Xavier Rebillard, Nadine Houédé
Prostate cancer is the most common malignant disease in men. Several therapeutic agents have been approved during the last 10 years. Among them, radium-223 dichloride (Xofigo(®)) is a radioactive isotope that induces irreversible DNA double-strand breaks and consequently tumor cell death. Radium-223 dichloride is a calcium-mimetic agent that specifically targets bone lesions. Radium-223 dichloride has been approved for the treatment of metastatic castration-resistant prostate cancer with symptomatic bone metastases, without known visceral metastases...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28919575/an-integrative-model-of-prostate-cancer-interaction-with-the-bone-microenvironment
#10
A Farhat, D Jiang, D Cui, E T Keller, T L Jackson
Despite advanced efforts in early diagnosis, aggressive surgical treatment, and use of targeted chemotherapies, the prognosis for many cancers is still dismal. This emphasizes the necessity to develop new strategies for understanding tumor growth and metastasis. Here we use a systems approach that combines mathematical modeling and numerical simulation to develop a predictive computational model for prostate cancer and its subversion of the bone microenvironment. This model simulates metastatic prostate cancer evolution, progressing from normal bone and hormone levels to quantifiable diseased states...
September 14, 2017: Mathematical Biosciences
https://www.readbyqxmd.com/read/28916657/tenascin-c-and-integrin-%C3%AE-9-mediate-interactions-of-prostate-cancer-with-the-bone-microenvironment
#11
Rebeca San Martin, Ravi Pathak, Antrix Jain, Sung Yun Jung, Susan G Hilsenbeck, María C Piña-Barba, Andrew G Sikora, Kenneth J Pienta, David R Rowley
Deposition of the extracellular matrix protein tenascin-C is part of the reactive stroma response, which has a critical role in prostate cancer progression. Here, we report that tenascin C is expressed in the bone endosteum and is associated with formation of prostate bone metastases. Metastatic cells cultured on osteo-mimetic surfaces coated with tenascin C exhibited enhanced adhesion and colony formation as mediated by integrin α9β1. In addition, metastatic cells preferentially migrated and colonized tenascin-C-coated trabecular bone xenografts in a novel system that employed chorioallantoic membranes of fertilized chicken eggs as host...
September 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28871082/stromal-and-epithelial-transcriptional-map-of-initiation-progression-and-metastatic-potential-of-human-prostate-cancer
#12
Svitlana Tyekucheva, Michaela Bowden, Clyde Bango, Francesca Giunchi, Ying Huang, Chensheng Zhou, Arrigo Bondi, Rosina Lis, Mieke Van Hemelrijck, Ove Andrén, Sven-Olof Andersson, R William Watson, Stephen Pennington, Stephen P Finn, Neil E Martin, Meir J Stampfer, Giovanni Parmigiani, Kathryn L Penney, Michelangelo Fiorentino, Lorelei A Mucci, Massimo Loda
While progression from normal prostatic epithelium to invasive cancer is driven by molecular alterations, tumor cells and cells in the cancer microenvironment are co-dependent and co-evolve. Few human studies to date have focused on stroma. Here, we performed gene expression profiling of laser capture microdissected normal non-neoplastic prostate epithelial tissue and compared it to non-transformed and neoplastic low-grade and high-grade prostate epithelial tissue from radical prostatectomies, each with its immediately surrounding stroma...
September 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28805551/bone-targeted-cabazitaxel-nanoparticles-for-metastatic-prostate-cancer-skeletal-lesions-and-pain
#13
Andrew S Gdowski, Amalendu Ranjan, Marjana R Sarker, Jamboor K Vishwanatha
AIM: The aim of this study was to develop a novel cabazitaxel bone targeted nanoparticle (NP) system for improved drug delivery to the bone microenvironment. MATERIALS & METHODS: Nanoparticles were developed using poly(D,L-lactic-co-glycolic acid) and cabazitaxel as the core with amino-bisphosphonate surface conjugation. Optimization of nanoparticle physiochemical properties, in vitro evaluation in prostate cancer cell lines and in vivo testing in an intraosseous model of metastatic prostate cancer was performed...
September 2017: Nanomedicine
https://www.readbyqxmd.com/read/28720900/low-frequency-ultrasound-induced-vegf-suppression-and-synergy-with-dendritic-cell-mediated-anti-tumor-immunity-in-murine-prostate-cancer-cells-in-vitro
#14
Wei Zhang, Wen-De Shou, Yan-Jun Xu, Wen-Kun Bai, Bing Hu
High tumor vascular endothelial growth factor (VEGF) levels are associated with poor treatment outcomes in prostate cancer (PCa), and immune deficiency in the PCa microenvironment, especially suppression of dendritic cell (DC) proliferation, has been confirmed. In this study, we (1) investigated whether VEGF participates in DC suppression in murine PCa cells (RM-1), (2) down-regulated VEGF expression using low-frequency ultrasound and microbubbles (UM), and (3) further explored any synergistic effect on immunological activation...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28698458/integrin-%C3%AE-v%C3%AE-3-signaling-in-tumor-induced-bone-disease
#15
REVIEW
Kristin A Kwakwa, Julie A Sterling
Tumor-induced bone disease is common among patients with advanced solid cancers, especially those with breast, prostate, and lung malignancies. The tendency of these cancers to metastasize to bone and induce bone destruction is, in part, due to alterations in integrin expression and signaling. Substantial evidence from preclinical studies shows that increased expression of integrin αvβ3 in tumor cells promotes the metastatic and bone-invasive phenotype. Integrin αvβ3 mediates cell adhesion to several extracellular matrix proteins in the bone microenvironment which is necessary for tumor cell colonization as well as the transmission of mechanical signals for tumor progression...
July 8, 2017: Cancers
https://www.readbyqxmd.com/read/28693897/connexins-important-players-in-the-dissemination-of-prostate-cancer-cells
#16
REVIEW
Jonathan Boucher, Arnaud Monvoisin, Justine Vix, Marc Mesnil, Dominique Thuringer, Françoise Debiais, Laurent Cronier
Over the past 50 years, increasing experimental evidences have established that connexins (Cxs) and gap junctional intercellular communication (GJIC) ensure an important role in both the onset and development of cancerous processes. In the present review, we focus on the impact of Cxs and GJIC during the development of prostate cancer (PCa), from the primary growth mainly localized in acinar glands and ducts to the distant metastasis mainly concentrated in bone. As observed in several other types of solid tumours, Cxs and especially Cx43 exhibit an ambivalent role with a tumour suppressor effect in the early stages and, conversely, a rather pro-tumoral profile for most of invasion and dissemination steps to secondary sites...
July 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28675788/proteomics-profiling-of-exosomes-from-primary-mouse-osteoblasts-under-proliferation-versus-mineralization-conditions-and-characterization-of-their-uptake-into-prostate-cancer-cells
#17
Mehmet Asim Bilen, Tianhong Pan, Yu-Chen Lee, Song-Chang Lin, Guoyu Yu, Jing Pan, David Hawke, Bih-Fang Pan, Jody Vykoukal, Kavanya Gray, Robert L Satcher, Gary E Gallick, Li-Yuan Yu-Lee, Sue-Hwa Lin
Osteoblasts communicate both with normal cells in the bone marrow and with tumor cells that metastasized to bone. Here we show that osteoblasts release exosomes, we termed osteosomes, which may be a novel mechanism by which osteoblasts communicate with cells in their environment. We have isolated exosomes from undifferentiated/proliferating (D0 osteosomes) and differentiated/mineralizing (D24 osteosomes) primary mouse calvarial osteoblasts. The D0 and D24 osteosomes were found to be vesicles of 130-140 nm by dynamic light scattering analysis...
July 18, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28600175/overcoming-immunosuppression-in-bone-metastases
#18
REVIEW
Zachary Z Reinstein, Sahithi Pamarthy, Vinay Sagar, Ricardo Costa, Sarki A Abdulkadir, Francis J Giles, Benedito A Carneiro
Bone metastases are present in up to 70% of advanced prostate and breast cancers and occur at significant rates in a variety of other cancers. Bone metastases can be associated with significant morbidity. The establishment of bone metastasis activates several immunosuppressive mechanisms. Hence, understanding the tumor-bone microenvironment is crucial to inform the development of novel therapies. This review describes the current standard of care for patients with bone metastatic disease and novel treatment options targeting the microenvironment...
May 12, 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28588081/intercellular-transmission-of-the-unfolded-protein-response-promotes-survival-and-drug-resistance-in-cancer-cells
#19
Jeffrey J Rodvold, Kevin T Chiu, Nobuhiko Hiramatsu, Julia K Nussbacher, Valentina Galimberti, Navin R Mahadevan, Karl Willert, Jonathan H Lin, Maurizio Zanetti
Increased protein translation in cells and various factors in the tumor microenvironment can induce endoplasmic reticulum (ER) stress, which initiates the unfolded protein response (UPR). We have previously reported that factors released from cancer cells mounting a UPR induce a de novo UPR in bone marrow-derived myeloid cells, macrophages, and dendritic cells that facilitates protumorigenic characteristics in culture and tumor growth in vivo. We investigated whether this intercellular signaling, which we have termed transmissible ER stress (TERS), also operates between cancer cells and what its functional consequences were within the tumor...
June 6, 2017: Science Signaling
https://www.readbyqxmd.com/read/28428279/interaction-between-tumor-cell-surface-receptor-rage-and-proteinase-3-mediates-prostate-cancer-metastasis-to-bone
#20
Mikhail G Kolonin, Anna Sergeeva, Daniela I Staquicini, Tracey L Smith, Christy A Tarleton, Jeffrey J Molldrem, Richard L Sidman, Serena Marchiò, Renata Pasqualini, Wadih Arap
Human prostate cancer often metastasizes to bone, but the biological basis for such site-specific tropism remains largely unresolved. Recent work led us to hypothesize that this tropism may reflect pathogenic interactions between RAGE, a cell surface receptor expressed on malignant cells in advanced prostate cancer, and proteinase 3 (PR3), a serine protease present in inflammatory neutrophils and hematopoietic cells within the bone marrow microenvironment. In this study, we establish that RAGE-PR3 interaction mediates homing of prostate cancer cells to the bone marrow...
June 15, 2017: Cancer Research
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