Tumor microenvironment mechanisms and bone metastatic disease progression of prostate cancer

Kang, Juening; Manna, Federico La; Bonollo, Francesco; Sampson, Natalie; Alberts, Ian; Mingels, Clemens; Afshar‐Oromieh, Ali; Thalmann, George N.; Karkampouna, Sofia

doi:10.1016/j.canlet.2022.01.015

Cited by 70 publications

(51 citation statements)

References 170 publications

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“… 42 Tumor-secreted factors orchestrate this process and contribute to a hospitable environment. 43 , 44 Moreover, tumor self-seeding can lead to colonization of circulating tumor cells (CTCs) in their primary tumor of origin. 45 These polyclonal tumor cells persist despite hormonal/systemic therapy, facilitating disease progression.…”

Section: Treatment Of the Primarymentioning

confidence: 99%

The current role of precision surgery in oligometastatic prostate cancer

et al. 2022

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Section: Treatment Of the Primarymentioning

confidence: 99%

The current role of precision surgery in oligometastatic prostate cancer

et al. 2022

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“…In the former, cancer cells that reached the bone/bone marrow microenvironment secrete factors that induce a net increase in osteoclast differentiation and activity. These factors can act directly [e.g., tumor necrosis factor-α, interleukin (IL)-6, and IL-1β], and/or indirectly [like parathyroid hormone-related protein (PTHrP)], through the promotion of osteoblastic expression of pro-osteoclastogenic factors such as receptor activator of nuclear factor κB (RANKL) and macrophage colony-stimulating factor (M-CSF) [26,[33][34][35] . The increase in osteoclast activity and differentiation leads to the degradation of bone matrix and the release of IGF-1, TGF-β, platelet-derived growth factor (PDGF), and bone morphogenetic proteins (BMPs) from it, which in turn stimulate tumor growth, thus creating a feed-forward loop, with bone cells, i.e., the osteolytic vicious cycle.…”

Section: Bone Metastases and The "Vicious Cycle"mentioning

confidence: 99%

“…In the osteosclerotic vicious cycle, cancer cells secrete a different set of proteins, including IGF-1, wingless-related integration site-1 (WNT-1) and WNT-3A, BMPs, and endothelin (ET)-1. These promote osteoblast differentiation and activity, leading to deposition of primary bone and production of growth factors [ 24 , 36 , 37 ] . Tumor growth is therefore fomented by osteoblasts, thus closing the osteosclerotic vicious cycle.…”

Section: Introductionmentioning

confidence: 99%

Liquid biopsies in primary and secondary bone cancers

Ucci¹,

Rucci²,

Ponzetti³

2022

Cancer Drug Resist

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Liquid biopsies are a powerful tool to non-invasively analyze tumor phenotype and progression as well as drug resistance. In the bone oncology field, liquid biopsies would be particularly important to develop, since standard biopsies can be very painful, dangerous (e.g., when found in proximity to the spinal cord), and hard to collect. In this review, we explore the recent advances in liquid biopsies in both primary (osteosarcoma and Ewing sarcoma) and secondary bone cancers (breast, prostate, and lung cancer-induced bone metastases), presenting their current role and highlighting their unexpressed potential, as well as the barriers limiting their possible adoption, including costs, scalability, reproducibility, and isolation methods. We discuss the use of circulating tumor cells, cell-free circulating tumor DNA, and extracellular vesicles for the purpose of improving diagnosis, prognosis, evaluation of therapy resistance, and driving therapy decisions in both primary and secondary bone malignancies.

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“…The mechanisms involved in mPC are still under investigation, but it commonly spreads to various sites such as lymph nodes, the liver, lungs, and the brain. Patients frequently present with multifocal metastases [ 3 ]. The bone, especially the axial skeleton, represents an exquisite homing site for prostate cancer cells due to its close proximity and rich reservoir of nutrients [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Nano-Hydroxyapatite/PLGA Mixed Scaffolds as a Tool for Drug Development and to Study Metastatic Prostate Cancer in the Bone

et al. 2023

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(1) Background: Three-dimensional (3D) in vitro, biorelevant culture models that recapitulate cancer progression can help elucidate physio-pathological disease cues and enhance the screening of more effective therapies. Insufficient research has been conducted to generate in vitro 3D models to replicate the spread of prostate cancer to the bone, a key metastatic site of the disease, and to understand the interplay between the key cell players. In this study, we aim to investigate PLGA and nano-hydroxyapatite (nHA)/PLGA mixed scaffolds as a predictive preclinical tool to study metastatic prostate cancer (mPC) in the bone and reduce the gap that exists with traditional 2D cultures. (2) Methods: nHA/PLGA mixed scaffolds were produced by electrospraying, compacting, and foaming PLGA polymer microparticles, +/− nano-hydroxyapatite (nHA), and a salt porogen to produce 3D, porous scaffolds. Physicochemical scaffold characterisation together with an evaluation of osteoblastic (hFOB 1.19) and mPC (PC-3) cell behaviour (RT-qPCR, viability, and differentiation) in mono- and co-culture, was undertaken. (3) Results: The results show that the addition of nHA, particularly at the higher-level impacted scaffolds in terms of mechanical and degradation behaviour. The nHA 4 mg resulted in weaker scaffolds, but cell viability increased. Qualitatively, fluorescent imaging of cultures showed an increase in PC-3 cells compared to osteoblasts despite lower initial PC-3 seeding densities. Osteoblast monocultures, in general, caused an upregulation (or at least equivalent to controls) in gene production, which was highest in plain scaffolds and decreased with increases in nHA. Additionally, the genes were downregulated in PC3 and co-cultures. Further, drug toxicity tests demonstrated a significant effect in 2D and 3D co-cultures. (4) Conclusions: The results demonstrate that culture conditions and environment (2D versus 3D, monoculture versus co-culture) and scaffold composition all impact cell behaviour and model development.

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Tumor microenvironment mechanisms and bone metastatic disease progression of prostate cancer

Cited by 70 publications

References 170 publications

The current role of precision surgery in oligometastatic prostate cancer

The current role of precision surgery in oligometastatic prostate cancer

Liquid biopsies in primary and secondary bone cancers

Nano-Hydroxyapatite/PLGA Mixed Scaffolds as a Tool for Drug Development and to Study Metastatic Prostate Cancer in the Bone

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