Emerging Players in Prostate Cancer–Bone Niche Communication

Furesi, Giulia; Rauner, Martina; Hofbauer, Lorenz C.

doi:10.1016/j.trecan.2020.09.006

Cited by 50 publications

(39 citation statements)

References 85 publications

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“…A better understanding of the EV-mediated systemic cross-talk between tumor cells and distant cells should aid in developing novel therapeutic approaches. For example, in lung and liver metastasis, exosomes exert their effect through immune cells and stromal cells 45,51 ; in the bone, they mainly modulate local stromal cells, osteoclasts, and osteoblasts 52,53 . In liver metastasis of pancreatic cancer, macrophages play an essential role in receiving and relaying signals from tumor cell-derived exosomes 45 .…”

Section: Discussionmentioning

confidence: 99%

In vitro and in vivo analysis of microvesicle-mediated metastasis using a bright, red-shifted bioluminescent reporter protein of extracellular vesicles

Zarea

Perez

Broadbent

et al. 2021

Preprint

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Cancer cells produce heterogeneous extracellular vesicles (EVs) as mediators of intercellular communication. Our study focused on a novel method to image EV subtypes and their biodistribution in vivo. Regardless of injection routes, we established that reporter EVs isolated from murine mammary carcinoma cells expressing PalmReNL, which utilizes bioluminescence resonance energy transfer (BRET), localized to the lungs. This new EV reporter allowed highly sensitive EV tracking in vitro and in vivo and enabled us to begin studies to understand the commonalities and functional differences of the EV subtypes. We demonstrated the early appearance of metastatic foci in the lungs of mammary tumor-bearing mice following multiple injections of the microvesicle (MV)-enriched fraction derived from mammary carcinoma cells. In addition, the results we present here show that tumor cell-derived MVs act on distant tissues through upregulating LC3 expression within the lung.

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Section: Discussionmentioning

confidence: 99%

In vitro and in vivo analysis of microvesicle-mediated metastasis using a bright, red-shifted bioluminescent reporter protein of extracellular vesicles

Zarea

Perez

Broadbent

et al. 2021

Preprint

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“…Fundamental for this premetastatic niche in bone is the education of osteoblasts and bone marrow cells. This results in relevant changes of the osteoblasts that will boost the chance of successful seeding of PCa cells upon arrival [44,45]. Once located in the bone, metastatic PCa cells will activate the osteoclasts by releasing osteolytic factors (TGF-β, PDGF, VEGF, M-CSF and RANKL (Figure 1)) [44].…”

Section: Bone Metastases In Mcrpcmentioning

confidence: 99%

“…This results in relevant changes of the osteoblasts that will boost the chance of successful seeding of PCa cells upon arrival [44,45]. Once located in the bone, metastatic PCa cells will activate the osteoclasts by releasing osteolytic factors (TGF-β, PDGF, VEGF, M-CSF and RANKL (Figure 1)) [44]. In addition, the tumor cells have the ability to mimic normal osteoblast activity (osteomimicry) by releasing the osteoblastic factors osteocalcin, ALP and BMPs (Figure 1) [44].…”

Section: Bone Metastases In Mcrpcmentioning

confidence: 99%

Radium-223 Treatment of Patients with Metastatic Castration Resistant Prostate Cancer: Biomarkers for Stratification and Response Evaluation

Zande

Oyen

Zwart

et al. 2021

Cancers

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Radium-223 dichloride ([223Ra]RaCl2; Ra-223) is a targeted alpha-emitting radiopharmaceutical which results in an overall survival and health related quality of life (HRQoL) benefit in symptomatic patients with metastatic castration resistant prostate cancer (mCRPC) and predominantly bone metastasis. Although effective, options to select patients who will derive treatment benefit and to monitor and predict treatment outcomes are limited. PSA response and radiographic evaluation are commonly used in mCRPC treatment assessment but are not informative in Ra-223 treated patients. Consequently, there is a clear need for predictive and prognostic tools. In this review, we discuss the physiology of bone metastases and the mechanism of action and efficacy of Ra-223 treatment, as well as offering an outline of current innovative prognostic and predictive biomarkers.

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“…Bone marrow is one of the richest and most diverse organs in terms of its cellular and biochemical composition. It contains numerous cell types, such as hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs), endothelial cells, macroph ages, osteoblasts, osteoclasts, immune cells, stromal cells, megakaryocytes, fibroblasts, and adipocytes [ 22 , 23 , 24 , 40 , 41 , 42 , 43 ]. This cellular milieu appears to provide an environment for DCCs to reside in a dormant state.…”

Section: Niche Cell Types and Signals That Induce Or Block Pca DCC Dormancy In The Bone Marrow Microenvironmentmentioning

confidence: 99%

Prostate Cancer Dormancy and Reactivation in Bone Marrow

Singh

Patel

et al. 2021

JCM

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Prostate cancer has a variable clinical course, ranging from curable local disease to lethal metastatic spread. Eradicating metastatic cells is a unique challenge that is rarely met with the available therapies. Thus, targeting prostate cancer cells in earlier disease states is a crucial window of opportunity. Interestingly, cancer cells migrate from their primary site during pre-cancerous and malignant phases to seed secondary organs. These cells, known as disseminated cancer cells (DCCs), may remain dormant for months or decades before activating to form metastases. Bone marrow, a dormancy-permissive site, is the major organ for housed DCCs and eventual metastases in prostate cancer. The dynamic interplay between DCCs and the primary tumor microenvironment (TME), as well as that between DCCs and the secondary organ niche, controls the conversion between states of dormancy and activation. Here, we discuss recent discoveries that have improved our understanding of dormancy signaling and the role of the TME in modulating the epigenetic reprogramming of DCCs. We offer potential strategies to target DCCs in prostate cancer.

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Emerging Players in Prostate Cancer–Bone Niche Communication

Cited by 50 publications

References 85 publications

In vitro and in vivo analysis of microvesicle-mediated metastasis using a bright, red-shifted bioluminescent reporter protein of extracellular vesicles

In vitro and in vivo analysis of microvesicle-mediated metastasis using a bright, red-shifted bioluminescent reporter protein of extracellular vesicles

Radium-223 Treatment of Patients with Metastatic Castration Resistant Prostate Cancer: Biomarkers for Stratification and Response Evaluation

Prostate Cancer Dormancy and Reactivation in Bone Marrow

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