Distinct Osteomimetic Response of Androgen‐Dependent and Independent Human Prostate Cancer Cells to Mechanical Action of Fluid Flow: Prometastatic Implications

González, Álvaro; Durango, Cira García de; Alonso, V.; Bravo, Beatriz; Gortázar, Arancha R.; Wells, Alan; Forteza, Jerónimo; Vidal‐Vanaclocha, Fernando

doi:10.1002/pros.23270

Cited by 16 publications

(9 citation statements)

References 56 publications

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“…All the experimental results in this study indicate osteoblastic bone formation by PC‐3 cells and osteolytic bone resorption by MDA PCa 2b, whereas PC‐3 is predominantly identified as osteolytic and MDA PCa 2b as osteoblastic in nature based on experiments at primary sites of cancer . ex vivo studies have demonstrated the osteoblastic characteristic of PC‐3 cells in a 3D cancer–bone model using a co‐culture of live calvarial bones and cancer cells .…”

Section: Discussionmentioning

confidence: 50%

Prostate Cancer Phenotype Influences Bone Mineralization at Metastasis: A Study Using an In Vitro Prostate Cancer Metastasis Testbed

et al. 2019

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In this study, two types of prostate cancer cell lines, highly metastatic PC‐3 and low metastatic MDA PCa 2b (PCa) were cultured on bone mimetic scaffolds to recapitulate metastasis to bone. A unique in vitro 3D tumor model that uses a sequential culture (SC) of human mesenchymal stem cells followed by seeding with cancer cells after bone formation was initiated to study the phenotype‐specific interaction between prostate cancer cells and bone microenvironment. The PCa cells were observed to be less prolific and less metastatic, and to form multicellular tumoroids in the bone microenvironment, whereas PC‐3 cells were more prolific and were highly metastatic, and did not form multicellular tumoroids in the bone microenvironment. The metastatic process exhibited by these two prostate cancer cell lines showed a significant and different effect on bone mineralization and extracellular matrix formation. Excessive bone formation in the presence of PC‐3 and significant osteolysis in the presence of PCa were observed, which was also indicated by osteocalcin and MMP‐9 expression as measured by ELISA and qRT‐PCR. The field emission scanning electron microscopy images revealed that the structure of mineralized collagen in the presence of PC‐3 is different than the one observed in healthy bone. All experimental results indicated that both osteolytic and osteoblastic bone lesions can be recapitulated in our tumor testbed model and that different cancer phenotypes have a very different influence on bone at metastasis. The 3D in vitro model presented in this study provides an improved, reproducible, and controllable system that is a useful tool to elucidate osteotropism of prostate cancer cells. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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Section: Discussionmentioning

confidence: 50%

Prostate Cancer Phenotype Influences Bone Mineralization at Metastasis: A Study Using an In Vitro Prostate Cancer Metastasis Testbed

et al. 2019

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“…At present, a large number of drugs, including abiraterone acetate, bicalutamide and cabazitaxel have been approved by the U.S. Food and Drug Administration for the treatment of human prostate cancer (3,4). Androgen deprivation therapy has demonstrated a degree of effectiveness against androgen-dependent prostate malignancies (5,6). However, as prostate cancer advances it frequently transforms into androgen-independent prostate cancer (AIPC), reducing the efficacy of androgen deprivation therapy (7).…”

Section: Introductionmentioning

confidence: 99%

Reduced pim‑1 expression increases chemotherapeutic drug sensitivity in human androgen‑independent prostate cancer cells by inducing apoptosis

et al. 2019

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Chemotherapeutic drug resistance is an obstacle for the successful therapy of prostate cancer. The aim of the present study was to identify the effects of proto-oncogene serine/threonine-protein kinase pim-1 (pim-1) in the proliferation of chemotherapeutic drug-resistant prostate cancer cells. Androgen-independent human prostate cancer cell lines PC3 and DU145 were used in the current study. Cisplatin-sensitive PC3 cells and cisplatin-resistant PC3/DDP cells were used in drug-resistance assays. The expression levels of pim-1, permeability glycoprotein (p-gp), caspase-3 and cleaved caspase-3 were determined using western blotting analysis; pim-1 was knocked down using pim-1-specific short hairpin RNA (shRNA); cell viability was determined using MTT assay and IC 50 values of the chemotherapeutic drugs in human prostate cancer cells tested were calculated using GraphPad 5 software. Androgen-independent human prostate cancer cell lines PC3 and DU145 were transfected with pim-1-targeted or control shRNA, and MTT results revealed that pim-1 knockdown significantly inhibited PC3 and DU145 cell viability in a time-dependent manner (P<0.01). Cisplatin-resistant cells PC3/DDP exhibited higher levels of pim-1 and p-gp expression compared with cisplatin-sensitive PC3 cells; and pim-1 knockdown markedly increased chemotherapeutic drug sensitivity in PC3/DDP cells. In addition, pim-1 knockdown increased chemotherapeutic drug sensitivity in PC3/DDP cells. The molecular mechanism of drug sensitivity was discovered to be partly due to pim-1 knockdown, as it significantly increased apoptosis in cisplatin-resistant PC3/DDP cells. The present study may provide a new strategy for the therapy of prostate cancer.

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“…In addition, PCa-derived EVs have been reported to play a role in metastatic bone remodeling including favoring the differentiation of osteoblasts, impairing the differentiation of osteoclasts, and driving osteomimicry of PCa cells in the bone microenvironment [43][44][45][46][47][48]. Intriguingly, integrins that are found in the exosomal cargo can be instrumental in organ-specific metastasis [49] and the transfer of αVβ6 integrins between PCa cells was shown to promote cell adhesion and migration [50].…”

Section: Pre-metastatic Niche (Sending a Reconnaissance Team Ahead Ofmentioning

confidence: 99%

How Prostate Cancer Cells Use Strategy Instead of Brute Force to Achieve Metastasis

Tharp

Nandana

2019

Cancers

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Akin to many other cancers, metastasis is the predominant cause of lethality in prostate cancer (PCa). Research in the past decade or so has revealed that although metastatic manifestation is a multi-step and complex process that is orchestrated by distinct cellular and molecular mechanisms, the process in itself is an extremely inefficient one. It is now becoming increasingly evident that PCa cells employ a plethora of strategies to make the most of this inefficient process. These strategies include priming the metastatic sites ahead of colonization, devising ways to metastasize to specific organs, outsmarting the host defense surveillance, lying in a dormant state at the metastatic site for prolonged periods, and widespread reprogramming of the gene expression to suit their needs. Based on established, recent, and evolving lines of research, this review is an attempt to understand PCa metastasis from the perspective of military combat, wherein strategic maneuvering instead of brute force often plays a decisive role in the outcome.

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Distinct Osteomimetic Response of Androgen‐Dependent and Independent Human Prostate Cancer Cells to Mechanical Action of Fluid Flow: Prometastatic Implications

Cited by 16 publications

References 56 publications

Prostate Cancer Phenotype Influences Bone Mineralization at Metastasis: A Study Using an In Vitro Prostate Cancer Metastasis Testbed

Prostate Cancer Phenotype Influences Bone Mineralization at Metastasis: A Study Using an In Vitro Prostate Cancer Metastasis Testbed

Reduced pim‑1 expression increases chemotherapeutic drug sensitivity in human androgen‑independent prostate cancer cells by inducing apoptosis

How Prostate Cancer Cells Use Strategy Instead of Brute Force to Achieve Metastasis

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