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Prostate cancer bone metastasis is the leading cause of cancer-related mortality in men in the United States, causing severe damage to skeletal tissue. The treatment of advanced-stage prostate cancer is always challenging due to limited drug treatment options, resulting in low survival rates. There is a scarcity of knowledge regarding the mechanisms associated with the effects of biomechanical cues by the interstitial fluid flow on prostate cancer cell growth and migration. We have designed a novel bioreactor system to demonstrate the impact of interstitial fluid flow on the migration of prostate cancer cells to the bone during extravasation. First, we demonstrated that a high flow rate induces apoptosis in PC3 cells via TGF-1 mediated signaling; thus, physiological flow rate conditions are optimum for cell growth. Next, to understand the role of interstitial fluid flow in prostate cancer migration, we evaluated the migration rate of cells under static and dynamic conditions in the presence or absence of bone. We report that CXCR4 levels were not significantly changed under static and dynamic conditions, indicating that CXCR4 activation in PC3 cells is not influenced by flow conditions but by the bone, where CXCR4 levels were upregulated. The bone-upregulated CXCR4 levels led to increased MMP-9 levels resulting in a high migration rate in the presence of bone. In addition, upregulated levels ofintegrins under fluid flow conditions contributed to an overall increase in the migration rate of PC3 cells. Overall, this study demonstrates the potential role of interstitial fluid flow in prostate cancer invasion. Understanding the critical role of interstitial fluid flow in promoting prostate cancer cell progression will enhance current therapies for advanced-stage prostate cancer and provide improved treatment options for patients.
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http://dx.doi.org/10.1088/1758-5090/acc09a | DOI Listing |
J Clin Invest
December 2024
Department of Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy.
PARP inhibitors (PARPi) have received regulatory approval for the treatment of several tumors, including prostate cancer (PCa), and demonstrate remarkable results in the treatment of castration-resistant prostate cancer (CRPC) patients characterized by defects in homologous recombination repair (HRR) genes. Preclinical studies showed that DNA repair genes (DRG) other than HRR genes may have therapeutic value in the context of PARPi. To this end, we performed multiple CRISPR/Cas9 screens in PCa cell lines using a custom sgRNA library targeting DRG combined with PARPi treatment.
View Article and Find Full Text PDFJ Nephrol
December 2024
Division of Nephrology, Cantonal Hospital Aarau, Aarau, Switzerland.
Glycoconj J
December 2024
Department of Urology, University of the Ryukyus Graduate School of Medicine, 207 Uehara, Nishihara, Nakagami-gun, Okinawa, 903-0215, Japan.
Stage-specific embryonic antigen-4 (SSEA-4) is a developmentally regulated antigen, while expression level of SSEA-4 and / or its synthase ST3GAL2 is associated with prognosis in various malignancies. We have reported a prominent increase of SSEA-4 in castration-resistant prostate cancer (CRPC) and its negative correlation with the androgen receptor (AR). Meanwhile, loss of AR has increased to approximately 30% with the growing use of androgen receptor signaling inhibitor for metastatic CRPC (mCRPC).
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
December 2024
Department of Urology, Tangdu Hospital, Fourth Military Medical University, No.569 Xinsi Road, Xi'an, 710038, Shaanxi, China.
Radiosensitivity is critical for clinical outcomes and overall survival of prostate cancer patients treated with irradiation. Ribociclib and NU7026 have been reported as radiosensitizers in cancer cells, but which are inadequately understood in prostate cancer cells. The present study was performed to investigate the effects of ribociclib, NU7026, and their combination on the radiosensitivity of prostate cancer cells.
View Article and Find Full Text PDFJ Cancer Res Clin Oncol
December 2024
Institute of Sports Medicine & Prevention, University Leipzig, Leipzig, Germany.
Purpose: The reduced cardiorespiratory fitness (CRF) and functional capacity following surgical procedures and during cancer treatments is a major risk factor for morbidity and mortality among patients with cancer. We aimed to assess the impact of endurance and combined resistance exercise interventions during the postoperative rehabilitation period for patients with colorectal, breast, and prostate cancer.
Methods: A systematic search was conducted in MEDLINE Pubmed, Web of Science, and Cochrane Library until October 2023 for randomized controlled trials that assessed exercise interventions (aerobic/endurance; resistance or combined training) on postoperative patients with cancer.
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