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College, Institute, or Department
Pathology and Microbiology
Dr. Rakesh K. Singh
Malignant tumors are inherently pro-inflammatory, and infiltrating leukocytes are thought to be critical for tumor maintenance and progression. Infiltrating cells and molecules driving tumor-associated inflammation have considerable potential as therapeutic targets, yet this area remains relatively under-explored. Neutrophils are the most prevalent leukocyte in the innate immune system and have been shown to play an essential role in cancer progression. Previously our lab has reported that as pancreatic ductal adenocarcinoma (PDAC) disease progresses, there is an increase in the infiltration of neutrophils. The specific objective of this study is to determine the role of neutrophil-PDAC cell interaction in therapy resistance. We analyzed whether direct neutrophil-PDAC cell interaction modulates their survival and whether it is dependent on therapy resistance. We used two human and murine neutrophil cell line models (MPRO and HL60) and two isogenic parent CD18/HPAF (C) and gemcitabine-resistant variant CD18/HPAF-R (CGR). Neutrophil and PDAC cells were co-cultured for 24 h, and their proliferation/survival was determined using WST and MTT assays. We observed that PDAC cancer cell proliferation increased when co-cultured with neutrophils. Moreover, cell free-neutrophil conditioned media modulated PDAC cell proliferation in a concentration-dependent (v/v) manner. We observed significantly higher proliferation in therapy-resistant CGR cell lines. Furthermore, our data suggest neutrophils co-cultured with therapy-resistant CGR cells had higher survival compared to neutrophils co-cultured with parent C cells. Together our data demonstrate that neutrophil-PDAC cell interaction modulates their proliferation and survival.
Pancreatic Cancer, Pancreatic ductal adenocarcinoma, therapy resistance, pro-tumorigenic tumor microenvironment, neutrophil recruitment, gemcitabine-resistant cell line, co-culture, conditioned media
Abrahams, Lauren; Sturgeon, Reegan; Maher, Michael; Tinsley, Parker; Johnson, Ester; and Singh, Rakesh K., "Gemcitabine Resistant PDAC Cell- Neutrophil Interaction Regulates their Proliferation and Survival" (2023). Posters: 2023 Summer Undergraduate Research Program. 10.