Keywords Prostate cancer bone microenvi...

Prostate cancer bone microenvironment
Eric Schwartz, Zachery Reichert, Catherine Van Poznak
Bone is a common site of metastases, particularly in advanced breast and prostate cancer. Skeletal related events associated with bone metastases include pathologic fracture, need for surgery/radiation to bone and cord compression. These events cause significant morbidity and mortality. Bisphosphonates as well as denosumab act on the bone microenvironment and reduce the rate of skeletal related events by approximately 25%-40%. Hence, these therapies are an important adjunctive therapy in cancer care. Despite the established efficacy and recommendations for their use in many international guidelines, these bone modifying agents are underutilized...
November 7, 2020: Bone
Manuel A Riquelme, Eduardo R Cardenas, Jean X Jiang
Bone is the most frequent site of breast cancer and prostate cancer metastasis, and one of the most common sites of metastasis for many solid tumors. Once cancer cells colonize in the bone, it imposes a major clinical challenge for the treatment of the disease, and fatality rates increase drastically. Bone, the largest organ in the body, provides a fertile microenvironment enriched with nutrients, growth factors and hormones, a generous reward for cancer cells. Dependent on cancer type, cancer cells can cause osteoblastic (bone forming) or osteolytic lesions to promote the net resorption and/or release of growth factors from the bone extracellular matrix...
2020: Frontiers in Endocrinology
Abhisha Sawant Dessai, Mayrel Palestino Dominguez, Uan-I Chen, John Hasper, Christian Prechtl, Cuijuan Yu, Eriko Katsuta, Tao Dai, Bokai Zhu, Sung Yun Jung, Nagireddy Putluri, Kazuaki Takabe, Xiang H-F Zhang, Bert W O'Malley, Subhamoy Dasgupta
Metabolic dysregulation is a known hallmark of cancer progression, yet the oncogenic signals that promote metabolic adaptations to drive metastatic cancer remain unclear. Here we show that transcriptional repression of mitochondrial deacetylase sirtuin 3 (SIRT3) by androgen receptor (AR) and its coregulator steroid receptor coactivator (SRC-2) enhances mitochondrial aconitase (ACO2) activity to favor aggressive prostate cancer. ACO2 promoted mitochondrial citrate synthesis to facilitate de novo lipogenesis, and genetic ablation of ACO2 reduced total lipid content and severely repressed in vivo prostate cancer progression...
October 28, 2020: Cancer Research
Ödül Karayazi Atıcı, Nayantara Govindrajan, Isbel Lopetegui-González, Carrie S Shemanko
Prolactin has a rich mechanistic set of actions and signaling in order to elicit developmental effects in mammals. Historically, prolactin has been appreciated as an endocrine peptide hormone that is responsible for final, functional mammary gland development and lactation. Multiple signaling pathways impacted upon by the microenvironment contribute to cell function and differentiation. Endocrine, autocrine and paracrine signaling are now apparent in not only mammary development, but also in cancer, and involve multiple cell types including those of the immune system...
October 24, 2020: Seminars in Cell & Developmental Biology
Wenjing Zhu, Dongya Sheng, Yiqun Shao, Qiang Zhang, Yu Peng
Advanced stage of prostate cancer cells preferentially metastasizes to varying bones of prostate cancer patients, resulting in incurable disease with poor prognosis and limited therapeutical treatment options. Calcitonin gene-related peptide (CGRP), a neuropeptide produced by prostate gland, is known to play a pivotal role in facilitating tumor growth and metastasis of numerous human cancers. In this study, we aim to investigate the clinical relevance of CGRP in prostate cancer patients and the effects of CGRP and CGRP antagonists on prostate tumor growth in the mouse model...
October 18, 2020: Peptides
Jonathan Boucher, Annie-Claire Balandre, Marjolaine Debant, Justine Vix, Thomas Harnois, Nicolas Bourmeyster, Elodie Péraudeau, Amandine Chépied, Jonathan Clarhaut, Françoise Debiais, Arnaud Monvoisin, Laurent Cronier
Among the different interacting molecules implicated in bone metastases, connexin43 (Cx43) may increase sensitivity of prostate cancer (PCa) cells to bone microenvironment, as suggested by our in silico and human tissue samples analyses that revealed increased level of Cx43 expression with PCa progression and a Cx43 specific expression in bone secondary sites. The goal of the present study was to understand how Cx43 influences PCa cells sensitivity and aggressiveness to bone microenvironment. By means of Cx43-overexpressing PCa cell lines, we revealed a Cx43-dependent promigratory effect of osteoblastic conditioned media (ObCM)...
October 16, 2020: Cancers
Robert E Coleman, Peter I Croucher, Anwar R Padhani, Philippe Clézardin, Edward Chow, Marie Fallon, Theresa Guise, Simone Colangeli, Rodolfo Capanna, Luis Costa
Bone is the most frequent site for metastasis for many cancers, notably for tumours originating in the breast and the prostate. Tumour cells can escape from the primary tumour site and colonize the bone microenvironment. Within the bone, these disseminated tumour cells, as well as those arising in the context of multiple myeloma, may assume a state of dormancy, remaining quiescent for years before resuming proliferation and causing overt metastasis, which causes bone destruction via activation of osteoclast-mediated osteolysis...
October 15, 2020: Nature Reviews. Disease Primers
Richard Karlsson, Per Larsson, Regina Miftakhova, Azharuddin Sajid Syed Khaja, Martuza Sarwar, Julius Semenas, Sa Chen, Andreas Hedblom, Tianyan Wang, Kristina Ekström-Holka, Athanasios Simoulis, Anjani Kumar, Niels Ødum, Thomas Grundström, Jenny L Persson
Cancer cells facilitate growth and metastasis by using multiple signals from the cancer-associated microenvironment. However, it remains poorly understood whether prostate cancer (PCa) cells may recruit and utilize bone marrow cells for their growth and survival. Furthermore, the regulatory mechanisms underlying interactions between PCa cells and bone marrow cells are obscure. In this study, we isolated bone marrow cells that mainly constituted populations that were positive for CD11b and Gr1 antigens from xenograft PC-3 tumor tissues from athymic nu/nu mice...
September 22, 2020: Cancers
Ushashi C Dadwal, Alyssa R Merkel, Jonathan M Page, Kristin A Kwakwa, Michael Kessler, Julie A Rhoades
Patients with advanced skeletal metastases arising from primary cancers including breast, lung, and prostate suffer from extreme pain, bone loss, and frequent fractures. While the importance of interactions between bone and tumors is well-established, our understanding of complex cell-cell and cell-microenvironment interactions remains limited in part due to a lack of appropriate 3D bone models. To improve our understanding of the influence of bone morphometric properties on the regulation of tumor-induced bone disease (TIBD), we utilized bone-like 3D scaffolds in vitro and in vivo...
September 21, 2020: International Journal of Molecular Sciences
Brendan Connell, Pavel Kopach, Wenying Ren, Raghav Joshi, Stephen Naber, Ming Zhou, Paul Mathew
Background: Collaborative signaling between fibronectin-binding αv and α5 integrins has been implicated in the lethal dissemination of prostate cancer in the bone-metastatic niche, the major source of morbidity and mortality in the disease. Methods: We assessed the frequency and pattern of expression of these integrins in primary high-grade adenocarcinomas and bone metastases compared to the physiological gland. Formalin-fixed paraffin-embedded (FFPE) radical prostatectomy (RP) samples (n=25) containing ≥ Gleason grade 4 cancer and decalcified surgical or diagnostic bone metastatic samples from 10 patients were stained for integrin αv (ITGAV) and integrin α5 (ITGA5) expression...
August 2020: Translational Andrology and Urology
Laura Carminati, Giulia Taraboletti
Thrombospondins (TSPs) are a family of five multimeric matricellular proteins. Through a wide range of interactions, TSPs play pleiotropic roles in embryogenesis and in tissue remodeling in adult physiology as well as in pathological conditions, including cancer development and metastasis. TSPs are active in bone remodeling, the process of bone resorption (osteolysis) and deposition (osteogenesis) that maintains bone homeostasis. TSPs are particularly involved in aberrant bone remodeling, including osteolytic and osteoblastic skeletal cancer metastasis, frequent in advanced cancers such as breast and prostate carcinoma...
September 16, 2020: American Journal of Physiology. Cell Physiology
Isaac J Powell, Sreenivasa R Chinni, Sunil S Reddy, Alexander Zaslavsky, Navnath Gavande
Pro-inflammatory cytokine and chemokines genes drive prostate cancer progression and metastasis: molecular mechanism update and the science that underlies racial disparity. comprehensive review article. Isaac J. Powell, S. Chinni, S.S. Reddy, Alexander Zaslavsky, Navnath Gavande Introduction: In 2013 we reported that with the use of bioinformatics and ingenuity pathway network analysis we were able to identify functional driver genes that were differentially expressed among a large population of African American men (AAM) and European American men (EAM)...
September 5, 2020: Urologic Oncology
Jeremy S Frieling, Tao Li, Marilena Tauro, Conor C Lynch
Bone metastatic prostate cancer significantly impacts patient quality of life and overall survival, and despite available therapies, it is presently incurable with an unmet need for improved treatment options. As mediators of tumor progression, matrix metalloproteinases (MMPs) can degrade extracellular matrix components and regulate growth factor and cytokine bioactivity. Depending on tissue context, MMPs can either promote or inhibit tumorigenesis. Therefore, it is essential to study individual MMPs in specific cancer contexts and microenvironments to support the design and application of selective MMP inhibitors...
September 4, 2020: Neoplasia: An International Journal for Oncology Research
Eugen Dhimolea, Ricardo de Matos Simoes, Dhvanir Kansara, Xiang Weng, Shruti Sharma, Pallavi Awate, Zhiyi Liu, Dong Gao, Nicholas Mitsiades, Joseph H Schwab, Yu Chen, Rinath Jeselsohn, Aedín C Culhane, Myles Brown, Irene Georgakoudi, Constantine S Mitsiades
Although hormonal therapy (HT) inhibits the growth of hormone receptor-positive (HR+) breast (BrCa) and prostate (PrCa) cancers, HT resistance frequently develops within the complex metastatic microenvironment of the host organ (often the bone), a setting poorly recapitulated in 2D culture systems. To address this limitation, we cultured HR+ BrCa and PrCa spheroids and patient-derived organoids in 3D extracellular matrices (ECM) alone or together with bone marrow stromal cells (BMSC). In 3D monocultures, antiestrogens and antiandrogens induced anoikis by abrogating anchorage-independent growth of HR+ cancer cells but exhibited only modest effects against tumor cells residing in the ECM niche...
August 28, 2020: Cancer Research
Julie Talbot, Maryne Dupuy, Sarah Morice, Françoise Rédini, Franck Verrecchia
Despite research and clinical advances during recent decades, bone cancers remain a leading cause of death worldwide. There is a low survival rate for patients with primary bone tumors such as osteosarcoma and Ewing's sarcoma or secondary bone tumors such as bone metastases from prostate carcinoma. Gap junctions are specialized plasma membrane structures consisting of transmembrane channels that directly link the cytoplasm of adjacent cells, thereby enabling the direct exchange of small signaling molecules between cells...
August 26, 2020: Biomolecules
Mathieu Borel, Giovanna Lollo, David Magne, René Buchet, Leyre Brizuela, Saida Mebarek
Prostate cancer (PCa) is the most frequent cancer in men aged 65 and over. PCa mainly metastasizes in the bone, forming osteosclerotic lesions, inducing pain, fractures, and nerve compression. Cancer cell-derived exosomes participate in the metastatic spread, ranging from oncogenic reprogramming to the formation of pre-metastatic niches. Moreover, exosomes were recently involved in the dialog between PCa cells and the bone metastasis microenvironment. Phospholipase D (PLD) isoforms PLD1/2 catalyze the hydrolysis of phosphatidylcholine to yield phosphatidic acid (PA), regulating tumor progression and metastasis...
August 12, 2020: Biochimica et Biophysica Acta. Molecular Basis of Disease
Jake P Taylor-King, Pascal R Buenzli, S Jon Chapman, Conor C Lynch, David Basanta
Advanced cancers, such as prostate and breast cancers, commonly metastasize to bone. In the bone matrix, dendritic osteocytes form a spatial network allowing communication between osteocytes and the osteoblasts located on the bone surface. This communication network facilitates coordinated bone remodeling. In the presence of a cancerous microenvironment, the topology of this network changes. In those situations, osteocytes often appear to be either overdifferentiated (i.e., there are more dendrites than healthy bone) or underdeveloped (i...
2020: Frontiers in Bioengineering and Biotechnology
Cuizhe Wang, Jingzhou Wang, Keru Chen, Huai Pang, Xue Li, Jiaojiao Zhu, Yinghua Ma, Tongtong Qiu, Wei Li, Jianxin Xie, Jun Zhang
Prostate cancer (PCa) continues to be the most common, noncutaneous cancer in men. Bone is the most frequent site of PCa metastases, and up to 90% of patients with advanced PCa develop bone metastases. An altered bone marrow microenvironment, induced by obesity, is a significant mediator for the bone tropism of PCa. However, the specific molecular mechanisms by which obesity causes changes in the bone marrow microenvironment, leading to PCa bone metastasis, are not fully understood. Our results demonstrate that a high fat diet (HFD) leads to dyslipidemia and changes in bone marrow of nude mice: an increased in the area and number of adipocytes and a reduction in the area and number of osteoblasts...
August 8, 2020: Cancer Science
Tania Velletri, Yin Huang, Yu Wang, Qing Li, Mingyuan Hu, Ningxia Xie, Qian Yang, Xiaodong Chen, Qing Chen, Peishun Shou, Yurun Gan, Eleonora Candi, Annicchiarico-Petruzzelli Margherita, Massimiliano Agostini, Huilin Yang, Gerry Melino, Yufang Shi, Ying Wang
p53 plays a pivotal role in controlling the differentiation of mesenchymal stem cells (MSCs) by regulating genes involved in cell cycle and early steps of differentiation process. In the context of osteogenic differentiation of MSCs and bone homeostasis, the osteoprotegerin/receptor activator of NF-κB ligand/receptor activator of NF-κB (OPG/RANKL/RANK) axis is a critical signaling pathway. The absence or loss of function of p53 has been implicated in aberrant osteogenic differentiation of MSCs that results in higher bone formation versus erosion, leading to an unbalanced bone remodeling...
July 21, 2020: Cell Death and Differentiation
Nicholas Spetsieris, Myrto Boukovala, Justin A Weldon, Alexandros Tsikkinis, Anh Hoang, Ana Aparicio, Shi-Ming Tu, John C Araujo, Amado J Zurita, Paul G Corn, Lance Pagliaro, Jeri Kim, Jennifer Wang, Sumit K Subudhi, Nizar M Tannir, Christopher J Logothetis, Patricia Troncoso, Xuemei Wang, Sijin Wen, Eleni Efstathiou
BACKGROUND: Resistance to novel androgen signaling inhibition and metastatic castration-resistant prostate cancer (mCRPC) progression is likely dependent on tumor microenvironment interactions. The Src pathway and neoangiogenesis have been implicated in prostate cancer progression. We studied the effect of adding the targeted agents dasatinib and sunitinib to abiraterone acetate (AA) in men with mCRPC. PATIENTS AND METHODS: In this open-label randomized phase 2 study, mCRPC patients received AA...
May 30, 2020: Clinical Genitourinary Cancer
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