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Prostate cancer bone microenvironment

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https://www.readbyqxmd.com/read/28600175/overcoming-immunosuppression-in-bone-metastases
#1
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
#2
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
#3
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...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28371333/behavior-of-prostate-cancer-cells-in-a-nanohydroxyapatite-collagen-bone-scaffold
#4
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
#5
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...
April 3, 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
#6
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 Halleen, Robert L Vessella, Arne Scholz
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. <br /><br />Experimental Design: Mice bearing intratibial LNCaP or LuCaP 58 tumors were randomized to groups (n = 12-17) based on lesion grade and/or serum PSA level and administered with radium-223 (300 kBq/kg) or vehicle, twice at 4-week intervals...
March 31, 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
#7
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-alphav-class-integrins-inhibits-prostate-cancer-progression
#8
Yuan Jiang, Jinlu Dai, Zhi Yao, Greg Shelley, Evan T Keller
Integrins that contain an integrin alpha V subunit contribute to multiple functions that promote cancer progression. The goal of this study was to determine if abituzumab (DI17E6, EMD 525797), a humanized monoclonal antibody (mAb) against integrin alpha V impacts, prostate cancer (PCa) progression. To evaluate this, PCa 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...
March 17, 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
#9
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
https://www.readbyqxmd.com/read/28253234/engineering-a-humanized-bone-organ-model-in-mice-to-study-bone-metastases
#10
Laure C Martine, Boris M Holzapfel, Jacqui A McGovern, Ferdinand Wagner, Verena M Quent, Parisa Hesami, Felix M Wunner, Cedryck Vaquette, Elena M De-Juan-Pardo, Toby D Brown, Bianca Nowlan, Dan Jing Wu, Cosmo Orlando Hutmacher, Davide Moi, Tatiana Oussenko, Elia Piccinini, Peter W Zandstra, Roberta Mazzieri, Jean-Pierre Lévesque, Paul D Dalton, Anna V Taubenberger, Dietmar W Hutmacher
Current in vivo models for investigating human primary bone tumors and cancer metastasis to the bone rely on the injection of human cancer cells into the mouse skeleton. This approach does not mimic species-specific mechanisms occurring in human diseases and may preclude successful clinical translation. We have developed a protocol to engineer humanized bone within immunodeficient hosts, which can be adapted to study the interactions between human cancer cells and a humanized bone microenvironment in vivo. A researcher trained in the principles of tissue engineering will be able to execute the protocol and yield study results within 4-6 months...
April 2017: Nature Protocols
https://www.readbyqxmd.com/read/28241871/a-loss-of-host-derived-mmp-7-promotes-myeloma-growth-and-osteolytic-bone-disease-in-vivo
#11
S T Lwin, J A Fowler, M T Drake, J R Edwards, C C Lynch, C M Edwards
Matrix metalloproteinases (MMPs) play a critical role in cancer pathogenesis, including tumor growth and osteolysis within the bone marrow microenvironment. However, the anti-tumor effects of MMPs are poorly understood, yet have significant implications for the therapeutic potential of targeting MMPs. Host derived MMP-7 has previously been shown to support the growth of bone metastatic breast and prostate cancer. In contrast and underscoring the complexity of MMP biology, here we identified a tumor-suppressive role for host MMP-7 in the progression of multiple myeloma in vivo...
February 28, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28223547/cabozantinib-targets-bone-microenvironment-modulating-human-osteoclast-and-osteoblast-functions
#12
Marco Fioramonti, Daniele Santini, Michele Iuliani, Giulia Ribelli, Paolo Manca, Nicola Papapietro, Filippo Spiezia, Bruno Vincenzi, Vincenzo Denaro, Antonio Russo, Giuseppe Tonini, Francesco Pantano
Cabozantinib, a c-MET and vascular endothelial growth factor receptor 2 inhibitor, demonstrated to prolong progression free survival and improve skeletal disease-related endpoints in castration-resistant prostate cancer and in metastatic renal carcinoma. Our purpose is to investigate the direct effect of cabozantinib on bone microenvironment using a total human model of primary osteoclasts and osteoblasts.Osteoclasts were differentiated from monocytes isolated from healthy donors; osteoblasts were derived from human mesenchymal stem cells obtained from bone fragments of orthopedic surgery patients...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28181686/the-effect-of-a-histone-deacetylase-inhibitor-ar-42-on-canine-prostate-cancer-growth-and-metastasis
#13
Said M Elshafae, Nicole A Kohart, Lucas A Altstadt, Wessel P Dirksen, Thomas J Rosol
BACKGROUND: Canine prostate cancer (PCa) is an excellent preclinical model for human PCa. AR-42 is a histone deacetylase inhibitor (HDACi) developed at The Ohio State University that inhibits the proliferation of several cancers, including multiple myeloma, lung, and hepatocellular cancer. In this study, we investigated whether AR-42 would prevent or decrease. The growth and metastasis of a canine PCa (Ace-1 cells) to bone in vitro and in vivo. METHODS: Proliferation, cell viability, invasion, and metastasis of a canine prostate cancer cell line (Ace-1) were measured following treatment with AR-42...
February 9, 2017: Prostate
https://www.readbyqxmd.com/read/28087740/bone-microenvironment-changes-in-latexin-expression-promote-chemoresistance
#14
Mi Zhang, Mary Osisami, Jinlu Dai, Jill M Keller, June Escara-Wilke, Atsushi Mizokami, Evan T Keller
Although docetaxel is the standard of care for advanced prostate cancer, most patients develop resistance to docetaxel. Therefore, elucidating the mechanism that underlies resistance to docetaxel is critical to enhance therapeutic intervention. Mining cDNA microarray from the PC-3 prostate cancer cell line and its docetaxel-resistant derivative (PC3-TxR) revealed decreased latexin (LXN) expression in the resistant cells. LXN expression was inversely correlated with taxane resistance in a panel of prostate cancer cell lines...
April 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28049638/leukemic-blasts-program-bone-marrow-adipocytes-to-generate-a-protumoral-microenvironment
#15
Manar S Shafat, Thomas Oellerich, Sebastian Mohr, Stephen D Robinson, Dylan R Edwards, Christopher R Marlein, Rachel E Piddock, Matthew Fenech, Lyubov Zaitseva, Amina Abdul-Aziz, Jeremy Turner, Johnathan A Watkins, Matthew Lawes, Kristian M Bowles, Stuart A Rushworth
Despite currently available therapies, most patients diagnosed with acute myeloid leukemia (AML) die of their disease. Tumor-host interactions are critical for the survival and proliferation of cancer cells; accordingly, we hypothesize that specific targeting of the tumor microenvironment may constitute an alternative or additional strategy to conventional tumor-directed chemotherapy. Because adipocytes have been shown to promote breast and prostate cancer proliferation, and because the bone marrow adipose tissue accounts for up to 70% of bone marrow volume in adult humans, we examined the adipocyte-leukemia cell interactions to determine if they are essential for the growth and survival of AML...
March 9, 2017: Blood
https://www.readbyqxmd.com/read/28029019/osteoblasts-are-the-centerpiece-of-the-metastatic-bone-microenvironment
#16
REVIEW
Hyo Min Jeong, Sun Wook Cho, Serk In Park
The tumor microenvironment is comprised of diverse stromal cell populations in addition to tumor cells. Increasing evidence now clearly supports the role of microenvironment stromal cells in tumor progression and metastasis, yet the regulatory mechanisms and interactions among tumor and stromal cells remain to be elucidated. Bone metastasis is the major problem in many types of human malignancies including prostate, breast and lung cancers, and the biological basis of bone metastasis let alone curative approaches are largely undetermined...
December 2016: Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27991924/cooperation-among-heterogeneous-prostate-cancer-cells-in-the-bone-metastatic-niche
#17
K Shahriari, F Shen, A Worrede-Mahdi, Q Liu, Y Gong, F U Garcia, A Fatatis
The growth of disseminated tumor cells into metastatic lesions depends on the establishment of a favorable microenvironment in the stroma of the target organs. Here we show that mice treated with anakinra, an antagonist of the interleukin (IL)-1β receptor (IL-1R), or harboring a targeted deletion of IL-1R are significantly less prone to develop bone tumors when inoculated in the arterial circulation with human prostate cancer (PCa) cells expressing IL-1β. Interestingly, human mesenchymal stem cells exposed in vitro to medium conditioned by IL-1β-expressing cancer cells responded by upregulating S100A4, a marker of cancer-associated fibroblasts (CAFs), and this effect was blocked by anakinra...
May 18, 2017: Oncogene
https://www.readbyqxmd.com/read/27843540/radium-223-and-metastatic-castration-resistant-prostate-cancer-all-that-glitters-is-not-gold
#18
REVIEW
Carlo Aprile, Marco G Persico, Lorenzo Lodola, Federica E Buroni
After being approved by the National Drug Agency in several countries, Radium-223 (Ra-223) is gaining wide acceptance in the treatment of bone metastatic castration resistant prostate cancer. The exact mechanism of action remain unclear: The established model of direct alpha-particle irradiation from the remodelling bone surface, where Ra-223 accumulates, surrounding the tumor foci can explain a lethal effect only on metastatic microdeposits, but not on higher tumor burden. According to the "pre-metastatic niche model", it is likely that Ra-223 targets several non-tumoral cell types of the tumor microenvironment involved in the complex mechanism of cancer bone homing and colonization...
October 28, 2016: World Journal of Radiology
https://www.readbyqxmd.com/read/27817214/antibody-therapeutics-for-treating-prostate-cancer-where-are-we-now-and-what-comes-next
#19
Panagiotis J Vlachostergios, Giuseppe Galletti, Jessica Palmer, Linda Lam, Beerinder S Karir, Scott T Tagawa
Progress in the understanding of molecular events of carcinogenesis and cancer evolution as well as the identification of tumor antigens has led to the development of different targeted therapeutic approaches, including the use of monoclonal antibodies (mAbs). Prostate cancer (PC) is highly amenable to mAb targeting given the existence of prostate-specific targets and the natural history and localization of metastatic disease. Areas covered: Several aspects of the PC phenotype, including growth factors, angiogenesis mediators, bone microenvironment signals, and immune evasion pathways, have become areas of ongoing investigation in terms of mAb targeting...
February 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/27813116/distinct-osteomimetic-response-of-androgen-dependent-and-independent-human-prostate-cancer-cells-to-mechanical-action-of-fluid-flow-prometastatic-implications
#20
Álvaro González, Cira García de Durango, Verónica Alonso, Beatriz Bravo, Arancha Rodríguez de Gortázar, Alan Wells, Jerónimo Forteza, Fernando Vidal-Vanaclocha
BACKGROUND AND METHODS: Prostate cancer frequently expresses an osteomimetic phenotype, but it is unclear how it is regulated and what biological and clinical implications it confers. Because mechanical forces physiologically regulate bone-remodeling activity in osteocytes, we hypothesized that mechanical action of fluid flow (MAFF) at the cancer microenvironment may similarly foster prostate cancer cell osteomimicry. RESULTS: We showed that in vitro MAFF on androgen-dependent (LNCap) and androgen-independent (PC3) prostate cancer cells remarkably increased OPG, VEGF, RunX2, PTH1R, and PTHrP gene expression in both cell lines irrespective of their androgen dependency...
November 3, 2016: Prostate
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