Preprint Article Version 1 This version is not peer-reviewed

Circulating Tumor Cells Develop Resistance to TRAIL-Induced Apoptosis through Autophagic Removal of Death Receptor 5: Evidence from an In Vitro Model

Version 1 : Received: 15 November 2018 / Approved: 19 November 2018 / Online: 19 November 2018 (06:44:04 CET)

A peer-reviewed article of this Preprint also exists.

Twomey, J.D.; Zhang, B. Circulating Tumor Cells Develop Resistance to TRAIL-Induced Apoptosis Through Autophagic Removal of Death Receptor 5: Evidence from an In Vitro Model. Cancers 2019, 11, 94. Twomey, J.D.; Zhang, B. Circulating Tumor Cells Develop Resistance to TRAIL-Induced Apoptosis Through Autophagic Removal of Death Receptor 5: Evidence from an In Vitro Model. Cancers 2019, 11, 94.

Journal reference: Cancers 2019, 11, 94
DOI: 10.3390/cancers11010094

Abstract

Circulating tumor cells (CTCs) in the peripheral blood are the precursors to distant metastasis but the underlying mechanisms are poorly understood.  This study aims at understanding the molecular features within CTCs in relation to their metastatic potential.  Using in vitro CTC models, in which breast cancer cell lines are cultured in non-adherent conditions simulating the microenvironment in the blood stream, we found that suspension culture resulted in resistance to TNF-related apoptosis inducing ligand (TRAIL)-mediated cell death. Such a resistance was directly correlated with a reduction in surface and total levels of DR5 protein. In the non-adherent state, cells underwent rapid autophagic flux characterized by an accumulation of autophagosome organelles. Notably, DR5 was translocated to autophagosomes and underwent lysosomal degradation.  Our data suggest that CTCs may evade TNF cytokine mediated immune surveillance through downregulation of DR expression. The data warrants further studies in cancer patients to find the status of DRs and other molecular features within primary CTCs in relation to disease progression or chemoresistance.

Subject Areas

circulating tumor cells; CTCs; breast cancer; metastasis; death receptor; TRAIL; apoptosis; in vitro model

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our diversity statement.

Leave a public comment
Send a private comment to the author(s)
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.