Bacterial cancer therapy in autochthonous colorectal cancer affects tumor growth and metabolic landscape

• DOI: 10.1172/jci.insight.139900
• Publication Date: 2021-10-28T16:00:23Z
• Authors: Gillian M. Mackie; Alastair Copland; Masumi Takahashi; Yumiko Nakanishi; Isabel Everard; Tamotsu Kato; Hirotsugu Oda; Takashi Kanaya; Hiroshi Ohno; Kendle M. Maslowski
• Keywords: Aroa; Organoid; Metabolome; Tumor initiation

Bacterial cancer therapy (BCT) shows great promise for treatment of solid tumors, yet basic mechanisms bacterial-induced tumor suppression remain undefined. Attenuated strains Salmonella enterica serovar Typhimurium (STm) have commonly been used in mouse models BCT xenograft and orthotopic transplant models. We aimed to better understand the epithelium–targeted by using autochthonous intestinal organoid cultures assess effectiveness consequences oral with aromatase A–deficient STm (STmΔaroA). STmΔaroA delivered gavage significantly reduced burden load both a colitis-associated colorectal (CAC) model spontaneous Apcmin/+ model. colonization tumors caused alterations transcription mRNAs associated stemness, epithelial-mesenchymal transition, cell cycle. Metabolomic analysis demonstrated alteration metabolic environment STmΔaroA-treated suggesting that imposes competition on tumor. Use vitro recapitulated effects seen mesenchymal markers, altered metabolome. Furthermore, live was required, demonstrating active including metabolite usage. is efficacious models, competition, has direct epithelium affecting stem cells.