The histogenetic origin of malignant cells predicts their cyto-toxicity towards synthetic lethality utilizing the TK.007 system

ABSTRACT: The efficacy of killing human cancer cells by a modified Herpes-simplex-virus thymidine kinase TK.007/ganciclovir (GCV) system was investigated in malignant cells of different histogenetic origin. The aim was to determine whether different histogenetic origins of cancer cells in them-selves influence their reaction towards an approach of synthetic lethality, which theoretically should be applicable independently of the cell type. Fifteen malignant human cell lines were transduced with a lentiviral vector to stably express the TK.007 gene and cell proliferation assays under GCV were performed. Among TK.007-expressing cell lines, lymphoma and leuke-mia cells were more susceptible to killing than solid cancer cells, while osteosarcoma and mela-noma cells exhibited an intermediate susceptibility. Similar differences in killing were also noted in wild-type non-transduced cells. This study highlights that the histogenetic origin of malignant cells strongly influences their susceptibility towards cytotoxic agents, with leukemias and lym-phomas being more sensitive than solid cancer cells.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Thomas Mair  

LAB HEAD: Udo Schumacher

PROVIDER: PXD052713 | Pride | 2025-01-17

REPOSITORIES: pride