Intratumoral magnetic hyperthermia in combination with 5-fluorouracil induces thrombogenic collagen fibers, cellular stress, and immune responses in heterotopic human colon cancer in mice

ABSTRACT: In this study we looked for the main protein pathway regulators which were responsible for the therapeutic impact on colon cancers when combining magnetic hyperthermia with the chemo-therapeutic agent 5-fluorouracil (5FU). In this context, chitosan-coated magnetic nanoparticles (MNP) functionalized with 5FU were intratumorally injected into subcutaneous human colon cancer xenografts (HT-29) in mice and exposed to an alternating magnetic field. A decreased tu-mor growth was found particularly for the combined thermo-chemotherapy vs. the correspond-ing monotherapies. By using computational analysis of the tumor proteome, we found upregu-lated functional pathway categories termed “cellular stress and injury”, “intracellular second messenger and nuclear receptor signaling”, “immune responses”, and “growth proliferation and development”. We predict TGF-beta, and other mediators, as important upstream regulators. In conclusion our findings show that the combined thermo-chemotherapy induces thrombogenic collagen fibers which are able to impair tumor nutrient supply. Further on, we associate several responses to the recognition of damage associated molecular patterns (DAMPs) by phagocytic cells, which immigrate into the tumor area. The activation of some pathways associated with cell survival implies the necessity to conduct multiple therapy sessions in connection with a corre-sponding monitoring, which could possibly be conducted on the base of the identified protein regulators.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Colon

DISEASE(S): Colon Cancer

SUBMITTER: Emilio Cirri  

LAB HEAD: Ingrid Hilger

PROVIDER: PXD027656 | Pride | 2021-11-10

REPOSITORIES: Pride