TRAIL-coated leukocytes to kill circulating tumor cells in the flowing blood from prostate cancer patients
Abstract Background Radical surgery is the first line treatment for localized prostate cancer (PC), however, several studies have demonstrated that surgical procedures induce tumor cell mobilization from the primary tumor into the bloodstream. Methods The number and temporal fluctuations of circulat...
Hlavní autoři: | , , , , , , , |
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Médium: | Článek |
Jazyk: | English |
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BMC
2021-08-01
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Edice: | BMC Cancer |
Témata: | |
On-line přístup: | https://doi.org/10.1186/s12885-021-08589-8 |
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author | Nerymar Ortiz-Otero Jocelyn R. Marshall Antonio Glenn Jubin Matloubieh Jean Joseph Deepak M. Sahasrabudhe Edward M. Messing Michael R. King |
author_facet | Nerymar Ortiz-Otero Jocelyn R. Marshall Antonio Glenn Jubin Matloubieh Jean Joseph Deepak M. Sahasrabudhe Edward M. Messing Michael R. King |
author_sort | Nerymar Ortiz-Otero |
collection | DOAJ |
description | Abstract Background Radical surgery is the first line treatment for localized prostate cancer (PC), however, several studies have demonstrated that surgical procedures induce tumor cell mobilization from the primary tumor into the bloodstream. Methods The number and temporal fluctuations of circulating tumor cells (CTC), cancer associated fibroblasts (CAF) and CTC cluster present in each blood sample was determined. Results The results show that both CTC and CTC cluster levels significantly increased immediately following primary tumor resection, but returned to baseline within 2 weeks post-surgery. In contrast, the CAF level decreased over time. In patients who experienced PC recurrence within months after resection, CTC, CAF, and cluster levels all increased over time. Based on this observation, we tested the efficacy of an experimental TNF-related apoptosis-inducing ligand (TRAIL)-based liposomal therapy ex-vivo to induce apoptosis in CTC in blood. The TRAIL-based therapy killed approximately 75% of single CTCs and CTC in cluster form. Conclusion Collectively, these data indicate that CTC cluster and CAF levels can be used as a predictive biomarker for cancer recurrence. Moreover, for the first time, we demonstrate the efficacy of our TRAIL-based liposomal therapy to target and kill prostate CTC in primary patient blood samples, suggesting a potential new adjuvant therapy to use in combination with surgery. |
first_indexed | 2024-12-19T21:16:05Z |
format | Article |
id | doaj.art-3a79c7292a1942c98a7db8edfffe4d0f |
institution | Directory Open Access Journal |
issn | 1471-2407 |
language | English |
last_indexed | 2024-12-19T21:16:05Z |
publishDate | 2021-08-01 |
publisher | BMC |
record_format | Article |
series | BMC Cancer |
spelling | doaj.art-3a79c7292a1942c98a7db8edfffe4d0f2022-12-21T20:05:20ZengBMCBMC Cancer1471-24072021-08-0121111210.1186/s12885-021-08589-8TRAIL-coated leukocytes to kill circulating tumor cells in the flowing blood from prostate cancer patientsNerymar Ortiz-Otero0Jocelyn R. Marshall1Antonio Glenn2Jubin Matloubieh3Jean Joseph4Deepak M. Sahasrabudhe5Edward M. Messing6Michael R. King7Meinig School of Biomedical Engineering, Cornell UniversityMeinig School of Biomedical Engineering, Cornell UniversityDepartment of Biomedical Engineering, Vanderbilt UniversityThe University of Rochester Medical CenterThe University of Rochester Medical CenterThe University of Rochester Medical CenterThe University of Rochester Medical CenterDepartment of Biomedical Engineering, Vanderbilt UniversityAbstract Background Radical surgery is the first line treatment for localized prostate cancer (PC), however, several studies have demonstrated that surgical procedures induce tumor cell mobilization from the primary tumor into the bloodstream. Methods The number and temporal fluctuations of circulating tumor cells (CTC), cancer associated fibroblasts (CAF) and CTC cluster present in each blood sample was determined. Results The results show that both CTC and CTC cluster levels significantly increased immediately following primary tumor resection, but returned to baseline within 2 weeks post-surgery. In contrast, the CAF level decreased over time. In patients who experienced PC recurrence within months after resection, CTC, CAF, and cluster levels all increased over time. Based on this observation, we tested the efficacy of an experimental TNF-related apoptosis-inducing ligand (TRAIL)-based liposomal therapy ex-vivo to induce apoptosis in CTC in blood. The TRAIL-based therapy killed approximately 75% of single CTCs and CTC in cluster form. Conclusion Collectively, these data indicate that CTC cluster and CAF levels can be used as a predictive biomarker for cancer recurrence. Moreover, for the first time, we demonstrate the efficacy of our TRAIL-based liposomal therapy to target and kill prostate CTC in primary patient blood samples, suggesting a potential new adjuvant therapy to use in combination with surgery.https://doi.org/10.1186/s12885-021-08589-8ProstatectomyCTC mobilizationCAFsCTC clusterCancer recurrenceTRAIL-liposomal therapy |
spellingShingle | Nerymar Ortiz-Otero Jocelyn R. Marshall Antonio Glenn Jubin Matloubieh Jean Joseph Deepak M. Sahasrabudhe Edward M. Messing Michael R. King TRAIL-coated leukocytes to kill circulating tumor cells in the flowing blood from prostate cancer patients BMC Cancer Prostatectomy CTC mobilization CAFs CTC cluster Cancer recurrence TRAIL-liposomal therapy |
title | TRAIL-coated leukocytes to kill circulating tumor cells in the flowing blood from prostate cancer patients |
title_full | TRAIL-coated leukocytes to kill circulating tumor cells in the flowing blood from prostate cancer patients |
title_fullStr | TRAIL-coated leukocytes to kill circulating tumor cells in the flowing blood from prostate cancer patients |
title_full_unstemmed | TRAIL-coated leukocytes to kill circulating tumor cells in the flowing blood from prostate cancer patients |
title_short | TRAIL-coated leukocytes to kill circulating tumor cells in the flowing blood from prostate cancer patients |
title_sort | trail coated leukocytes to kill circulating tumor cells in the flowing blood from prostate cancer patients |
topic | Prostatectomy CTC mobilization CAFs CTC cluster Cancer recurrence TRAIL-liposomal therapy |
url | https://doi.org/10.1186/s12885-021-08589-8 |
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