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...

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Hlavní autoři: Nerymar Ortiz-Otero, Jocelyn R. Marshall, Antonio Glenn, Jubin Matloubieh, Jean Joseph, Deepak M. Sahasrabudhe, Edward M. Messing, Michael R. King
Médium: Článek
Jazyk:English
Vydáno: BMC 2021-08-01
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.
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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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