Monocyte-Macrophage Differentiation Suppresses the Expression of Proapoptotic Receptors to Apo2L/TRAIL and Increases Resistance to TRAIL-Induced Apoptosis

Evstratova, Yana; Kobyakova, M. I.; Novikova, V. V.; Сенотов, А. С.; Акатов, В. С.; Фадеев, Р. С.

doi:10.1134/s0006350919050038

Cited by 3 publications

(3 citation statements)

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“…It is known that the differentiation of leukemic cells by exogenous factors can initiate their resistance to TRAIL-mediated apoptosis [ 8 , 9 , 10 , 11 ]. We assumed that the appearance of a macrophage-like phenotype in the THP-1ad cells might be accompanied by an increase in their resistance to TRAIL-induced cell death.…”

Section: Resultsmentioning

confidence: 99%

“…The acquisition by leukemic myeloid cells of macrophage-like phenotype signs can increase their resistance to TRAIL-induced apoptosis [ 8 , 9 , 10 , 11 ]. Usually, this phenomenon for leukemic cells is described as a response to the action of exogenous differentiating factors.…”

Section: Discussionmentioning

confidence: 99%

“…The induction of granulocytic differentiation in promyelocytic leukemia HL-60 cells by dimethyl sulfoxide (DMSO) can be accompanied by an increase in their TRAIL-resistance [10]. Apparently, the appearance of the signs of differentiation in leukemic cells induced by exogenic stimuli is consistent with the formation of resistance to TRAIL-mediated apoptosis within them [11]. The human leukemia THP-1 cell line is a well-known in vitro cell model for the immune modulation approach.…”

Section: Introductionmentioning

confidence: 99%

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Macrophage-like THP-1 Cells Derived from High-Density Cell Culture Are Resistant to TRAIL-Induced Cell Death via Down-Regulation of Death-Receptors DR4 and DR5

et al. 2022

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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) is a highly selective and promising anticancer agent due to its specific apoptosis-inducing effect on tumor cells, rather than most normal cells. TRAIL is currently under investigation for use in the treatment of leukemia. However, the resistance of leukemic cells to TRAIL-induced apoptosis may limit its efficacy. The mechanisms of leukemic cell resistance to antitumor immunity remains a topical issue. In this work, we have found an increase in the resistance to TRAIL-induced cell death in human leukemia THP-1 cells, which was caused by differentiation into a macrophage-like phenotype in high-density culture in vitro. Stressful conditions, manifested by the inhibition of cell growth and the activation of cell death in high-density culture of THP-1 cells, induced the appearance of cells adhered to culture dishes. The THP-1ad cell line was derived by selection of these adhered cells. The genetic study, using STR and aCGH assays, has shown that THP-1ad cells were derived from THP-1 cells due to mutagenesis. The THP-1ad cells possessed high proliferative potential and a macrophage-like immunophenotype. The adhesion of THP-1ad cells to the extracellular matrix was mediated by αVβ5 integrin. The cytokine production, as well as the rise of intracellular ROS and NO activities by LPS in THP-1ad cell culture, were characteristic of macrophage-like cells. The THP-1ad cells were found to appear to increase in resistance to TRAIL-induced cell death in comparison with THP-1 cells. The mechanism of the increase in TRAIL-resistance can be related to a decrease in the expression of death receptors DR4 and DR5 on the THP-1ad cells. Thus, the macrophage-like phenotype formation with the maintenance of a high proliferative potential of leukemic cells, caused by stress conditions in high-density cell cultures in vitro, can induce an increase in resistance to TRAIL-induced cell death due to the loss of DR4 and DR5 receptors. The possible realization of these events in vivo may be the reason for tumor progression.

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