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Prostate cancer bone microenvironment

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https://www.readbyqxmd.com/read/29661810/metastases-in-prostate-cancer
#1
Federico La Manna, Sofia Karkampouna, Eugenio Zoni, Marta De Menna, Janine Hensel, George N Thalmann, Marianna Kruithof-de Julio
Prostate cancer (PCa) prognosis and clinical outcome is directly dependent on metastatic occurrence. The bone microenvironment is a favorable metastatic niche. Different biological processes have been suggested to contribute to the osteotropism of PCa such as hemodynamics, bone-specific signaling interactions, and the "seed and soil" hypothesis. However, prevalence of disseminating tumor cells in the bone is not proportional to the actual occurrence of metastases, as not all patients will develop bone metastases...
April 16, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/29600344/size-matters-metastatic-cluster-size-and-stromal-recruitment-in-the-establishment-of-successful-prostate-cancer-to-bone-metastases
#2
Arturo Araujo, Leah M Cook, Conor C Lynch, David Basanta
Prostate cancer (PCa) impacts over 180,000 men every year in the USA alone, with 26,000 patients expected to succumb to the disease ( cancer.gov ). The primary cause of death is metastasis, with secondary lesions most commonly occurring in the skeleton. Prostate cancer to bone metastasis is an important, yet poorly understood, process that is difficult to explore with experimental techniques alone. To this end we have utilized a hybrid (discrete-continuum) cellular automaton model of normal bone matrix homeostasis that allowed us to investigate how metastatic PCa can disrupt the bone microenvironment...
March 29, 2018: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/29593201/adipose-tissue-critical-contributor-to-the-development-of-prostate-cancer
#3
Uehara Hisanori, Tomoko Kobayashi, Minoru Matsumoto, Shunsuke Watanabe, Akiko Yoneda, Bando Yoshimi
The prostate is surrounded by periprostatic adipose tissue. Although adipose tissue was thought to play limited physiological roles, it has recently been recognized as an active endocrine organ, secreting growth factors and adipokines. Epidemiologically, obesity is associated with prostate cancer progression. A major mechanism to explain the link between obesity and cancer includes the insulin and insulin-like growth factor (IGF)-1 axis, sex steroids, and adipokines. When prostate cancer cells invade periprostatic adipose tissue, adipose tissue contributes to create the tumor microenvironment, mainly via adipokine secretion...
2018: Journal of Medical Investigation: JMI
https://www.readbyqxmd.com/read/29553053/bone-targeted-therapies-to-reduce-skeletal-morbidity-in-prostate-cancer
#4
Tanya B Dorff, Neeraj Agarwal
Bone metastases are the main driver of morbidity and mortality in advanced prostate cancer. Targeting the bone microenvironment, a key player in the pathogenesis of bone metastasis, has become one of the mainstays of therapy in men with advanced prostate cancer. This review will evaluate the data supporting the use of bone-targeted therapy, including (1) bisphosphonates such as zoledronic acid, which directly target osteoclasts, (2) denosumab, a receptor activator of nuclear factor-kappa B (RANK) ligand inhibitor, which targets a key component of bone stromal interaction, and (3) radium-223, an alpha-emitting calcium mimetic, which hones to the metabolically active areas of osteoblastic metastasis and induces double-strand breaks in the DNA...
March 16, 2018: Asian Journal of Andrology
https://www.readbyqxmd.com/read/29527701/identification-of-an-il-1-induced-gene-expression-pattern-in-ar-pca-cells-that-mimics-the-molecular-phenotype-of-ar-pca-cells
#5
Shayna E Thomas-Jardin, Mohammed S Kanchwala, Joan Jacob, Sana Merchant, Rachel K Meade, Nagham M Gahnim, Afshan F Nawas, Chao Xing, Nikki A Delk
BACKGROUND: In immunosurveillance, bone-derived immune cells infiltrate the tumor and secrete inflammatory cytokines to destroy cancer cells. However, cancer cells have evolved mechanisms to usurp inflammatory cytokines to promote tumor progression. In particular, the inflammatory cytokine, interleukin-1 (IL-1), is elevated in prostate cancer (PCa) patient tissue and serum, and promotes PCa bone metastasis. IL-1 also represses androgen receptor (AR) accumulation and activity in PCa cells, yet the cells remain viable and tumorigenic; suggesting that IL-1 may also contribute to AR-targeted therapy resistance...
March 11, 2018: Prostate
https://www.readbyqxmd.com/read/29514796/osteoblast-secreted-factors-mediate-dormancy-of-metastatic-prostate-cancer-in-the-bone-via-activation-of-the-tgf%C3%AE-riii-p38mapk-ps249-t252rb-pathway
#6
Li-Yuan Yu-Lee, Guoyu Yu, Yu-Chen Lee, Song-Chang Lin, Jing Pan, Tianhong Pan, Kai-Jie Yu, Bin Liu, Chad J Creighton, Jaime Rodriguez-Canales, Pamela Andrea Villalobos, Ignacio Ivan Wistuba, Eulàlia de Nadal, Francesc Posas, Gary E Gallick, Sue-Hwa Lin
Bone metastasis from prostate cancer (PCa) can occur years after prostatectomy, due to reactivation of dormant disseminated tumor cells (DTC) in the bone, yet the mechanism by which DTC are initially induced into a dormant state in the bone remains to be elucidated. We show here that the bone microenvironment confers dormancy to C4-2B4 PCa cells, as they become dormant when injected into mouse femurs but not under the skin. Live-cell imaging of dormant cells at the single cell level revealed that conditioned medium from differentiated, but not undifferentiated osteoblasts induced C4-2B4 cellular quiescence, suggesting that differentiated osteoblasts present locally around the tumor cells in the bone conferred dormancy to PCa cells...
March 7, 2018: Cancer Research
https://www.readbyqxmd.com/read/29507684/tumor-microenvironment-promotes-prostate-cancer-cell-dissemination-via-the-akt-mtor-pathway
#7
Junlin Shi, Lihui Wang, Chunlin Zou, Yudui Xia, Siyuan Qin, Evan Keller, Atsushi Mizokami, Jian Zhang, Yi Lu
Metastasis causes high mortality in various malignancies, including prostate cancer (PCa). Accumulating data has suggested that cancer cells spread from the primary tumor to distant sites at early stage, which is characterized by disseminated tumor cells (DTCs). However, lack of direct evidence of partial localized PCa cells occurring epithelial-to-mesenchymal transition (EMT) and disseminating to distant sites (e.g bone marrow). In this study, we used luciferase labeled PCa cells to establish an EMT mouse model and to detect whether DTCs spread into the bone marrow...
February 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29497363/parathyroid-hormone-related-peptide-elicits-peripheral-trpv1-dependent-mechanical-hypersensitivity
#8
Andrew J Shepherd, Aaron D Mickle, Suraj Kadunganattil, Hongzhen Hu, Durga P Mohapatra
Bone metastasis in breast, prostate and lung cancers often leads to chronic pain, which is poorly managed by existing analgesics. The neurobiological mechanisms that underlie chronic pain associated with bone-metastasized cancers are not well understood, but sensitization of peripheral nociceptors by tumor microenvironment factors has been demonstrated to be important. Parathyroid hormone-related peptide (PTHrP) is highly expressed in bone-metastasized breast and prostate cancers, and is critical to growth and proliferation of these tumors in the bone tumor microenvironment...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29380085/current-perspectives-on-bone-metastases-in-castrate-resistant-prostate-cancer
#9
REVIEW
Christopher Logothetis, Michael J Morris, Robert Den, Robert E Coleman
Prostate cancer is the most frequent noncutaneous cancer occurring in men. On average, men with localized prostate cancer have a high 10-year survival rate, and many can be cured. However, men with metastatic castrate-resistant prostate cancer have incurable disease with poor survival despite intensive therapy. This unmet need has led to recent advances in therapy aimed at treating bone metastases resulting from prostate cancer. The bone microenvironment lends itself to metastases in castrate-resistant prostate cancer, as a result of complex interactions between the microenvironment and tumor cells...
January 29, 2018: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/29337106/loss-of-tgf-%C3%AE-signaling-in-osteoblasts-increases-basic-fgf-and-promotes-prostate-cancer-bone-metastasis
#10
Xiangqi Meng, Alexandra Vander Ark, Paul Daft, Erica Woodford, Jie Wang, Zachary Madaj, Xiaohong Li
TGF-β plays a central role in prostate cancer (PCa) bone metastasis, and it is crucial to understand the bone cell-specific role of TGF-β signaling in this process. Thus, we used knockout (KO) mouse models having deletion of the Tgfbr2 gene specifically in osteoblasts (Tgfbr2Col1CreERT KO) or in osteoclasts (Tgfbr2LysMCre KO). We found that PCa-induced bone lesion development was promoted in the Tgfbr2Col1CreERT KO mice, but was inhibited in the Tgfbr2LysMCre KO mice, relative to their respective control Tgfbr2FloxE2 littermates...
April 1, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29311669/adipocyte-activated-oxidative-and-er-stress-pathways-promote-tumor-survival-in-bone-via-upregulation-of-heme-oxygenase-1-and-survivin
#11
Mackenzie K Herroon, Erandi Rajagurubandara, Jonathan D Diedrich, Elisabeth I Heath, Izabela Podgorski
Metastatic tumor cells engage the local tumor microenvironment and activate specific pro-survival mechanisms to thrive and progress in the harsh bone marrow niche. Here we show that the major contributors to the survival of carcinoma cells that have colonized the bone marrow are the adipocyte-induced oxidative stress and ER stress pathways. We demonstrate that upon exposure to adipocyte-rich environments in vitro or in vivo, bone-trophic prostate and breast tumor cells upregulate the oxidative stress enzyme, HO-1...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29300334/understanding-the-progression-of-bone-metastases-to-identify-novel-therapeutic-targets
#12
REVIEW
Annie Schmid-Alliana, Heidy Schmid-Antomarchi, Rasha Al-Sahlanee, Patricia Lagadec, Jean-Claude Scimeca, Elise Verron
Bone is one of the most preferential target site for cancer metastases, particularly for prostate, breast, kidney, lung and thyroid primary tumours. Indeed, numerous chemical signals and growth factors produced by the bone microenvironment constitute factors promoting cancer cell invasion and aggression. After reviewing the different theories proposed to provide mechanism for metastatic progression, we report on the gene expression profile of bone-seeking cancer cells. We also discuss the cross-talk between the bone microenvironment and invading cells, which impacts on the tumour actions on surrounding bone tissue...
January 4, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29288523/c-c-motif-ligand-5-promotes-migration-of-prostate-cancer-cells-in-the-prostate-cancer-bone-metastasis-microenvironment
#13
Satoko Urata, Kouji Izumi, Kaoru Hiratsuka, Aerken Maolake, Ariunbold Natsagdorj, Kazuyoshi Shigehara, Hiroaki Iwamoto, Suguru Kadomoto, Tomoyuki Makino, Renato Naito, Yoshifumi Kadono, Wen-Jye Lin, Guzailinuer Wufuer, Kazutaka Narimoto, Atsushi Mizokami
Chemokines and their receptors have key roles in cancer progression. The present study investigated chemokine activity in the prostate cancer bone metastasis microenvironment. Growth and migration of human prostate cancer cells were assayed in cocultures with bone stromal cells. The migration of LNCaP cells significantly increased when co-cultured with bone stromal cells isolated from prostate cancer bone metastases. Cytokine array analysis of conditioned medium from bone stromal cell cultures identified CCL5 as a concentration-dependent promoter of LNCaP cell migration...
March 2018: Cancer Science
https://www.readbyqxmd.com/read/29212270/exosomal-mir-141-3p-regulates-osteoblast-activity-to-promote-the-osteoblastic-metastasis-of-prostate-cancer
#14
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
#15
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
#16
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
#17
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...
February 2018: Calcified Tissue International
https://www.readbyqxmd.com/read/29080972/the-proteasome-and-myeloma-associated-bone-disease
#18
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
#19
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
#20
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
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