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. Cancers2019, 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.
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. Cancers2019, 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.
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.
Keywords
circulating tumor cells; CTCs; breast cancer; metastasis; death receptor; TRAIL; apoptosis; in vitro model
Subject
Biology and Life Sciences, Cell and Developmental Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
