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Prostate cancer bone microenvironment

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https://www.readbyqxmd.com/read/27843540/radium-223-and-metastatic-castration-resistant-prostate-cancer-all-that-glitters-is-not-gold
#1
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
#2
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...
November 20, 2016: 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
#3
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
#4
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
#5
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...
November 2016: Anticancer Research
https://www.readbyqxmd.com/read/27782035/cancer-cell-colonisation-in-the-bone-microenvironment
#6
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
#7
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...
October 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27761367/the-role-of-micrornas-in-bone-metastasis
#8
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
#9
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
https://www.readbyqxmd.com/read/27684203/how-to-study-basement-membrane-stiffness-as-a-biophysical-trigger-in-prostate-cancer-and-other-age-related-pathologies-or-metabolic-diseases
#10
Mercedes Rodriguez-Teja, Claudia Breit, Mitchell Clarke, Kamil Talar, Kai Wang, Mohammad A Mohammad, Sage Pickwell, Guillermina Etchandy, Graeme J Stasiuk, Justin Sturge
Here we describe a protocol that can be used to study the biophysical microenvironment related to increased thickness and stiffness of the basement membrane (BM) during age-related pathologies and metabolic disorders (e.g. cancer, diabetes, microvascular disease, retinopathy, nephropathy and neuropathy). The premise of the model is non-enzymatic crosslinking of reconstituted BM (rBM) matrix by treatment with glycolaldehyde (GLA) to promote advanced glycation endproduct (AGE) generation via the Maillard reaction...
September 20, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27672740/paracrine-sonic-hedgehog-signaling-contributes-significantly-to-acquired-steroidogenesis-in-the-prostate-tumor-microenvironment
#11
Amy A Lubik, Mannan Nouri, Sarah Truong, Mazyar Ghaffari, Hans H Adomat, Eva Corey, Michael E Cox, Na Li, Emma S Guns, Parvin Yenki, Steven Pham, Ralph Buttyan
Despite the substantial benefit of androgen deprivation therapy (ADT) for metastatic prostate cancer, patients often progress to castration-resistant disease (CRPC) that is more difficult to treat. CRPC is associated with renewed androgen receptor activity in tumor cells and restoration of tumor androgen levels through acquired intratumoral steroidogenesis (AIS). Although prostate cancer (PCa) cells have been shown to have steroidogenic capability in vitro, we previously found that benign prostate stromal cells (PrSCs) can also synthesize testosterone (T) from an adrenal precursor, DHEA, when stimulated with a hedgehog (Hh) pathway agonist, SAG...
January 15, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27618899/molecular-mechanisms-of-bone-metastasis-which-targets-came-from-the-bench-to-the-bedside
#12
REVIEW
Sandra Casimiro, Arlindo R Ferreira, André Mansinho, Irina Alho, Luis Costa
Bone metastases ultimately result from a complex interaction between cancer cells and bone microenvironment. However, prior to the colonization of the bone, cancer cells must succeed through a series of steps that will allow them to detach from the primary tumor, enter into circulation, recognize and adhere to specific endothelium, and overcome dormancy. We now know that as important as the metastatic cascade, tumor cells prime the secondary organ microenvironment prior to their arrival, reflecting the existence of specific metastasis-initiating cells in the primary tumor and circulating osteotropic factors...
August 27, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27597110/re-bone-metastasis-in-prostate-cancer-recurring-mitochondrial-dna-mutation-reveals-selective-pressure-exerted-by-the-bone%C3%A2-microenvironment
#13
Anthony Atala
No abstract text is available yet for this article.
September 2016: Journal of Urology
https://www.readbyqxmd.com/read/27566487/the-role-of-the-microenvironment-in-prostate-cancer-associated-bone-disease
#14
REVIEW
Christina J Turner, Claire M Edwards
The bone is a common site for metastasis in patients with advanced prostate carcinoma, and provides a 'fertile' milieu which stimulates tumour growth and associated bone disease. For years, the concept of treatment strategies has remained targeting the tumour itself; however, the occurrence of chemoresistance remains a challenge now more than ever. The attraction of targeting the bone microenvironment in order to disrupt tumour localisation and proliferation stems from the idea that stromal cells are superiorly stable at a genetic level, thus decreasing the risk of resistance manifestation...
October 2016: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/27542256/assessing-angiogenic-responses-induced-by-primary-human-prostate-stromal-cells-in-a-three-dimensional-fibrin-matrix-assay
#15
W Nathaniel Brennen, Huong Nguyen, Susan L Dalrymple, Stephanie Reppert-Gerber, Jeesun Kim, John T Isaacs, Hans Hammers
Accurate modeling of angiogenesis in vitro is essential for guiding the preclinical development of novel anti-angiogenic agents and treatment strategies. The formation of new blood vessels is a multifactorial and multi-stage process dependent upon paracrine factors produced by stromal cells in the local microenvironment. Mesenchymal stem cells (MSCs) are multipotent cells in adults that can be recruited to sites of inflammation and tissue damage where they aid in wound healing through regenerative, trophic, and immunomodulatory properties...
August 17, 2016: Oncotarget
https://www.readbyqxmd.com/read/27498716/acidic-extracellular-ph-promotes-prostate-cancer-bone-metastasis-by-enhancing-pc-3-stem-cell-characteristics-cell-invasiveness-and-vegf-induced-vasculogenesis-of-bm-epcs
#16
Sheng Huang, Yubo Tang, Xinsheng Peng, Xingdong Cai, Qingde Wa, Dong Ren, Qiji Li, Jiaquan Luo, Liangping Li, Xuenong Zou, Shuai Huang
Bone metastasis is a main cause of cancer-related mortality in patients with advanced prostate cancer. Emerging evidence suggests that the acidic extracellular microenvironment plays significant roles in the growth and metastasis of tumors. However, the effects of acidity on bone metastasis of PCa remain undefined. In the present study, PC-3 cells were cultured in acidic medium (AM; pH 6.5) or neutral medium (NM; pH 7.4), aiming to investigate the effects and possible mechanisms of acidic extracellular microenvironment in bone metastasis of PCa...
October 2016: Oncology Reports
https://www.readbyqxmd.com/read/27492023/nanoparticle-mediated-sirna-delivery-assessed-in-a-3d-co-culture-model-simulating-prostate-cancer-bone-metastasis
#17
Kathleen A Fitzgerald, Jianfeng Guo, Rosanne M Raftery, Irene Mencía Castaño, Caroline M Curtin, Matt Gooding, Raphael Darcy, Fergal J O' Brien, Caitriona M O' Driscoll
siRNA has emerged as a potential therapeutic for the treatment of prostate cancer but effective delivery remains a major barrier to its clinical application. This study aimed to develop and characterise a 3D in vitro co-culture model to simulate prostate cancer bone metastasis and to assess the ability of the model to investigate nanoparticle-mediated siRNA delivery and gene knockdown. PC3 or LNCaP prostate cancer cells were co-cultured with hFOB 1.19 osteoblast cells in 2D on plastic tissue culture plates and in 3D on collagen scaffolds mimicking the bone microenvironment...
September 25, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27471491/bone-marrow-adipose-tissue-a-new-player-in-cancer-metastasis-to-bone
#18
REVIEW
Emma V Morris, Claire M Edwards
The bone marrow is a favored site for a number of cancers, including the hematological malignancy multiple myeloma, and metastasis of breast and prostate cancer. This specialized microenvironment is highly supportive, not only for tumor growth and survival but also for the development of an associated destructive cancer-induced bone disease. The interactions between tumor cells, osteoclasts and osteoblasts are well documented. By contrast, despite occupying a significant proportion of the bone marrow, the importance of bone marrow adipose tissue is only just emerging...
2016: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/27458427/new-3d-culture-approaches-to-study-interactions-of-bone-marrow-adipocytes-with-metastatic-prostate-cancer-cells
#19
Mackenzie Katheryn Herroon, Jonathan Driscoll Diedrich, Izabela Podgorski
Adipocytes are a major component of the bone marrow that can critically affect metastatic progression in bone. Understanding how the marrow fat cells influence growth, behavior, and survival of tumor cells requires utilization of in vitro cell systems that can closely mimic the physiological microenvironment. Herein, we present two new three-dimensional (3D) culture approaches to study adipocyte-tumor cell interactions in vitro. The first is a transwell-based system composed of the marrow-derived adipocytes in 3D collagen I gels and reconstituted basement membrane-overlayed prostate tumor cell spheroids...
2016: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/27450806/abrogation-of-prostaglandin-e-ep4-signaling-in-osteoblasts-prevents-the-bone-destruction-induced-by-human-prostate-cancer-metastases
#20
Kenta Watanabe, Tsukasa Tominari, Michiko Hirata, Chiho Matsumoto, Takayuki Maruyama, Gillian Murphy, Hideaki Nagase, Chisato Miyaura, Masaki Inada
The metastasis of tumors to bone is known to be promoted by prostaglandin E2 (PGE2) produced by the tumor host stromal tissue. Although bone metastases frequently occur in prostate cancer patients, the significance of PGE2 in stromal responses to the tumor is not known. In this study, we report that PGE2 and its receptor EP4 play a pivotal role in bone destruction and metastasis in an experimental metastasis model of prostate cancer in nude mice. Using human prostate cancer PC-3 cells that are stably transfected with luciferase, we showed that the development of bone metastasis was accompanied by increased osteoclastic bone resorption in the bone metastasis microenvironment, and could be abrogated by an EP4 receptor antagonist...
September 9, 2016: Biochemical and Biophysical Research Communications
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