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Prostate cancer bone microenvironment

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https://www.readbyqxmd.com/read/28333143/molecular-insights-of-gas6-tam-in-cancer-development-and-therapy
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28181686/the-effect-of-a-histone-deacetylase-inhibitor-ar-42-on-canine-prostate-cancer-growth-and-metastasis
#7
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
#8
Mi Zhang, Mary Osisami, Jinlu Dai, Jill M Keller, June Escara-Wilke, Atsushi Mizokami, Evan T Keller
Although docetaxel (DOX) is the standard of care for advanced prostate cancer (PCa), most patients develop resistance to DOX. Therefore, elucidating the mechanism that underlies resistance to DOX is critical to enhance therapeutic intervention. Mining cDNA microarray from the PC-3 PCa cell line and its DOX-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 PCa cell lines. LXN knockdown conferred DOX resistance to PCa cells in vitro and in vivo; whereas LXN overexpression reduced DOX resistance in several PCa cell lines...
January 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28049638/leukemic-blasts-program-bone-marrow-adipocytes-to-generate-a-pro-tumoral-microenvironment
#9
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 hypothesise that specific targeting of the tumor microenvironment may constitute an alternative or additional strategy to conventional tumor-directed chemotherapy. Since adipocytes have been shown to promote breast and prostate cancer proliferation, and because the bone marrow adipose tissue (MAT) accounts for up to 70% of bone marrow volume in adult humans, we examined the adipocyte-leukaemia cell interactions to determine if they are essential for the growth and survival of AML...
January 3, 2017: Blood
https://www.readbyqxmd.com/read/28029019/osteoblasts-are-the-centerpiece-of-the-metastatic-bone-microenvironment
#10
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
#11
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...
December 19, 2016: Oncogene
https://www.readbyqxmd.com/read/27843540/radium-223-and-metastatic-castration-resistant-prostate-cancer-all-that-glitters-is-not-gold
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/27809841/pharmacological-targeting-of-cxcl12-cxcr4-signaling-in-prostate-cancer-bone-metastasis
#15
M Katie Conley-LaComb, Louie Semaan, Rajareddy Singareddy, Yanfeng Li, Elisabeth I Heath, Seongho Kim, Michael L Cher, Sreenivasa R Chinni
BACKGROUND: The CXCL12/CXCR4 axis transactivates HER2 and promotes intraosseous tumor growth. To further explore the transactivation of HER2 by CXCL12, we investigated the role of small GTP protein Gαi2 in Src and HER2 phosphorylation in lipid raft membrane microdomains and the significance of CXCR4 in prostate cancer bone tumor growth. METHODS: We used a variety of methods such as lipid raft isolation, invasion assays, an in vivo model of intratibial tumor growth, bone histomorphometry, and immunohistochemistry to determine the role of CXCR4 signaling in lipid raft membrane microdomains and effects of targeting of CXCR4 for bone tumor growth...
November 3, 2016: Molecular Cancer
https://www.readbyqxmd.com/read/27793893/radium-223-insight-and-perspectives-in-bone-metastatic-castration-resistant-prostate-cancer
#16
REVIEW
Federica Eleonora Buroni, Marco Giovanni Persico, Francesca Pasi, Lorenzo Lodola, Rosanna Nano, Carlo Aprile
(223)Ra prolongs overall survival in symptomatic patients affected by multiple bone-metastatic castration-resistant prostatic cancer, without visceral or nodal involvement. However, many questions remain about its mechanisms of action, and its use in clinical practice is still unresolved. First of all, what is the main target of alpha-particle emission, that is, in what way does it influences the tumor microenvironment? When is the best timing in the course of the disease, extending its use to asymptomatic low-volume or even to the micrometastatic phase? What are suitable biomarkers to be employed as prognostic factors and response indicators? Which associations with other drugs and their sequence can offer the best results, and is their effect additive or synergistic? Ultimately, in the current climate of spending review, what is the optimal cost and benefit ratio regarding available treatments? In this review, we tried to answer these questions by analyzing the available scientific literature...
2016: Anticancer Research
https://www.readbyqxmd.com/read/27782035/cancer-cell-colonisation-in-the-bone-microenvironment
#17
REVIEW
Casina Kan, Geoffrey Vargas, François Le Pape, Philippe Clézardin
Bone metastases are a common complication of epithelial cancers, of which breast, prostate and lung carcinomas are the most common. The establishment of cancer cells to distant sites such as the bone microenvironment requires multiple steps. Tumour cells can acquire properties to allow epithelial-to-mesenchymal transition, extravasation and migration. Within the bone metastatic niche, disseminated tumour cells may enter a dormancy stage or proliferate to adapt and survive, interacting with bone cells such as hematopoietic stem cells, osteoblasts and osteoclasts...
October 4, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27776343/estrogen-related-receptor-alpha-in-castration-resistant-prostate-cancer-cells-promotes-tumor-progression-in-bone
#18
Anais Fradet, Mathilde Bouchet, Carine Delliaux, Manon Gervais, Casina Kan, Claire Benetollo, Francesco Pantano, Geoffrey Vargas, Lamia Bouazza, Martine Croset, Yohann Bala, Xavier Leroy, Thomas J Rosol, Jennifer Rieusset, Akeila Bellahcène, Vincent Castronovo, Jane E Aubin, Philippe Clézardin, Martine Duterque-Coquillaud, Edith Bonnelye
Bone metastases are one of the main complications of prostate cancer and they are incurable. We investigated whether and how estrogen receptor-related receptor alpha (ERRα) is involved in bone tumor progression associated with advanced prostate cancer. By meta-analysis, we first found that ERRα expression is correlated with castration-resistant prostate cancer (CRPC), the hallmark of progressive disease. We then analyzed tumor cell progression and the associated signaling pathways in gain-of-function/loss-of-function CRPC models in vivo and in vitro...
November 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27761367/the-role-of-micrornas-in-bone-metastasis
#19
Eugenio Zoni, Gabri van der Pluijm
The skeleton represents a common site of metastases for osteotropic cancers such as prostate and breast tumors and novel therapeutic targets and new markers for the monitoring of bone lesions are urgently needed. The formation of bone metastases is a complex process that starts at the level of the confined tumor and that is characterized by a dynamic crosstalk between the primary cancer and the future metastatic site, the bone. Factors released by the primary tumor contribute to prepare a fertile "soil", where a "pre-metastatic niche" is established prior to future colonization by cancer cells...
September 2016: Journal of Bone Oncology
https://www.readbyqxmd.com/read/27711225/keratin-13-is-enriched-in-prostate-tubule-initiating-cells-and-may-identify-primary-prostate-tumors-that-metastasize-to-the-bone
#20
Sandy Liu, Radu M Cadaneanu, Baohui Zhang, Lihong Huo, Kevin Lai, Xinmin Li, Colette Galet, Tristan R Grogan, David Elashoff, Stephen J Freedland, Matthew Rettig, William J Aronson, Beatrice S Knudsen, Michael S Lewis, Isla P Garraway
BACKGROUND: Benign human prostate tubule-initiating cells (TIC) and aggressive prostate cancer display common traits, including tolerance of low androgen levels, resistance to apoptosis, and microenvironment interactions that drive epithelial budding and outgrowth. TIC can be distinguished from epithelial and stromal cells that comprise prostate tissue via cell sorting based upon Epcam, CD44, and CD49f antigenic profiles. Fetal prostate epithelial cells (FC) possess a similar antigenic profile to adult TIC and are capable of inducing tubule formation...
2016: PloS One
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