Exosomal KRAS mutation promotes the formation of tumor-associated neutrophil extracellular traps and causes deterioration of colorectal cancer by inducing IL-8 expression

• DOI: 10.1186/s12964-020-0517-1
• Publication Date: 2020-03-30T16:04:09Z
• Authors: Anquan Shang; Chenzheng Gu; Chen Zhou; Yibao Yang; Chen Chen; Bingjie Zeng; Junlu Wu; Wenying Lu; Weiwei Wang; Zujun Sun; Dong Li
• Keywords: Neutrophil Extracellular Traps; Exosome

Abstract Background Colorectal cancer (CRC) remains one of the leading causes cancer-related death. The current study aimed to elucidate mechanism by which exosomes carrying KRAS mutant contribute neutrophil recruitment as well formation extracellular trap (NET) in CRC. Methods APC-WT and APC-KRAS G12D mouse models were initially developed. Peripheral blood, spleen, bone marrow (BM) mesenteric lymph nodes (mLN) isolated detect content. Then, mice injected with from mice. ratio neutrophils, NETs IL-8 protein content subsequently quantified colon tissues. DKs-8 (wild type) DKO-1 (KRAS mutant) cells employed for vitro experimentation. cultured exosome-treated PMA stimulated neutrophil-forming culture medium, cell viability, invasion, migration, adhesion evaluated. Results Compared mice, numbers polyps neutrophils peripheral spleen mLNs increased accompanied NET formation, expression exosomes. Meanwhile, upregulation, observed derived . investigation results revealed that more formed presence DKO-1-Exos, inhibited DNAse. In addition, DKs-8- cells-derived could adhere under static conditions vitro. Exosomal mutants noted exert stimulatory effects on production promote growth CRC cells. Conclusion provide evidence suggesting may transfer recipient trigger increases production, NETs, eventually deterioration