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Prostate cancer bone microenvironment

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https://www.readbyqxmd.com/read/28981962/the-bmp-antagonist-noggin-is-produced-by-osteoblasts-in-response-to-the-presence-of-prostate-cancer-cells
#1
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
#2
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...
September 25, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28919714/radium-223-dichloride-for-prostate-cancer-treatment
#3
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
#4
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
#5
Rebeca San Martin, Ravi Pathak, Antrix Jain, Sung Yun Jung, Susan G Hilsenbeck, Maria C Piňa-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 involved 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. Additionally, 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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/28371333/behavior-of-prostate-cancer-cells-in-a-nanohydroxyapatite-collagen-bone-scaffold
#15
Susana Cruz-Neves, Nilza Ribeiro, Inês Graça, Carmen Jerónimo, Susana R Sousa, Fernando J Monteiro
Prostate cancer (PCa) is the second leading cause of death among men in Europe and U.S. The metastatic dissemination pattern of PCa is unique, developing bone metastasis as the only site of progression, consequently with a prognosis very poor. The cancer cells interactions within the surrounding bone environment are critical for tumor growth and progression. Secreted protein, acidic and rich in cysteine (SPARC) is described to be involved in PCa cells migration and invasion into bone. Three-dimensional (3D) in vitro systems that are able to closely resemble the in vivo microenvironment are recently taking importance in cancer research...
March 28, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28368419/%C3%AE-np63%C3%AE-promotes-adhesion-of-metastatic-prostate-cancer-cells-to-the-bone-through-regulation-of-cd82
#16
V Di Giacomo, T V Tian, A Mas, M Pecoraro, L Batlle-Morera, L Noya, J Martín-Caballero, J Ruberte, W M Keyes
ΔNp63α is a critical mediator of epithelial development and stem cell function in a variety of tissues including the skin and breast, while overexpression of ΔNp63α acts as an oncogene to drive tumor formation and cancer stem cell properties in squamous cell carcinoma. However, with regards to the prostate, while ΔNp63α is expressed in the basal stem cells of the mature gland, during adenocarcinoma development, its expression is lost and its absence is used to clinically diagnose the malignant state. Surprisingly, here we identify a sub-population of bone metastatic prostate cancer cells in the PC3 cell line that express ΔNp63α...
August 2017: Oncogene
https://www.readbyqxmd.com/read/28364014/radium-223-inhibits-osseous-prostate-cancer-growth-by-dual-targeting-of-cancer-cells-and-bone-microenvironment-in-mouse-models
#17
Mari I Suominen, Katja M Fagerlund, Jukka P Rissanen, Yvonne M Konkol, Jukka P Morko, ZhiQi Peng, Esa J Alhoniemi, Salla K Laine, Eva Corey, Dominik Mumberg, Karl Ziegelbauer, Sanna-Maria Käkönen, Jussi M Halleen, Robert L Vessella, Arne Scholz
Purpose: Radium-223 dichloride (radium-223, Xofigo), a targeted alpha therapy, is currently used for the treatment of patients with castration-resistant prostate cancer (CRPC) with bone metastases. This study examines the mode-of-action and antitumor efficacy of radium-223 in two prostate cancer xenograft models.Experimental Design: Mice bearing intratibial LNCaP or LuCaP 58 tumors were randomized into groups (n = 12-17) based on lesion grade and/or serum PSA level and administered radium-223 (300 kBq/kg) or vehicle, twice at 4-week intervals...
August 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28333143/molecular-insights-of-gas6-tam-in-cancer-development-and-therapy
#18
REVIEW
Guiling Wu, Zhiqiang Ma, Wei Hu, Dongjin Wang, Bing Gong, Chongxi Fan, Shuai Jiang, Tian Li, Jianyuan Gao, Yang Yang
Since growth arrest-specific gene 6 (Gas6) was discovered in 1988, numerous studies have highlighted the role of the Gas6 protein and its receptors Tyro3, Axl and Mer (collectively referred to as TAM), in proliferation, apoptosis, efferocytosis, leukocyte migration, sequestration and platelet aggregation. Gas6 has a critical role in the development of multiple types of cancers, including pancreatic, prostate, oral, ovarian and renal cancers. Acute myelocytic leukaemia (AML) is a Gas6-dependent cancer, and Gas6 expression predicts poor prognosis in AML...
March 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28314844/abituzumab-targeting-of-%C3%AE-v-class-integrins-inhibits-prostate-cancer-progression
#19
Yuan Jiang, Jinlu Dai, Zhi Yao, Greg Shelley, Evan T Keller
Integrins that contain an integrin αV subunit contribute to multiple functions that promote cancer progression. The goal of this study was to determine whether abituzumab (DI17E6, EMD 525797), a humanized monoclonal antibody (mAb) against integrin αV impacts, prostate cancer progression. To evaluate this, prostate cancer cells were treated with DI17E6 and its effects on proliferation, apoptosis, cell-cycle, adhesion, detachment, migration, invasion and phosphorylation of downstream targets, including FAK, Akt, and ERK, were determined...
July 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28292438/maoa-dependent-activation-of-shh-il6-rankl-signaling-network-promotes-prostate-cancer-metastasis-by-engaging-tumor-stromal-cell-interactions
#20
Jason Boyang Wu, Lijuan Yin, Changhong Shi, Qinlong Li, Peng Duan, Jen-Ming Huang, Chunyan Liu, Fubo Wang, Michael Lewis, Yang Wang, Tzu-Ping Lin, Chin-Chen Pan, Edwin M Posadas, Haiyen E Zhau, Leland W K Chung
Metastasis is a predominant cause of death for prostate cancer (PCa) patients; however, the underlying mechanisms are poorly understood. We report that monoamine oxidase A (MAOA) is a clinically and functionally important mediator of PCa bone and visceral metastases, activating paracrine Shh signaling in tumor-stromal interactions. MAOA provides tumor cell growth advantages in the bone microenvironment by stimulating interleukin-6 (IL6) release from osteoblasts, and triggers skeletal colonization by activating osteoclastogenesis through osteoblast production of RANKL and IL6...
March 13, 2017: Cancer Cell
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