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Pathology and Microbiology
Tumor-promoting inflammation is a hallmark of cancer that contributes to tumor cells' survival and proliferation. Infiltrating leukocytes and pro-inflammatory cytokines released into the tumor microenvironment (TME) often cause this inflammation, which is often pro-tumorigenic. Neutrophils are one of the most abundant types of leukocytes found in circulation. Enhanced neutrophil infiltration into the TME with disease progression was previously observed in my lab. Neutrophils are a pro-tumorigenic and pro-metastatic part of the TME. It has been shown in previous research that neutrophils aid in PDAC progression and metastasis. Although, exact mechanisms of this neutrophil-PDAC interaction remain relatively unknown. The specific objective of this project is to determine the role of tumor-associated neutrophils in PDAC progression and metastasis. Our working hypothesis is that neutrophil-PDAC interaction increases PDAC proliferation, survival, and metastasis. The two neutrophil cell lines that were used in this study were mouse neutrophils, MPRO, and human neutrophils, HL-60. The two human pancreatic cancer cell lines that were used are L3.3 and L3.6. The pancreatic cancer cell line L3.3 is a low metastatic cell line while L3.6 is a high metastatic line. Cancer cells were either treated with neutrophil-conditioned media (indirect interaction), or co-cultured with the neutrophil (direct interaction). MTT assays were performed to analyze proliferation of the cancer cell lines, and a WST assay was performed to analyze the survival of neutrophils. We observed concentration-dependent increase in PDAC cell proliferation following treatment with neutrophil-conditioned media. Similarly, co-culture of PADC cell with neutrophils enhanced their proliferation. We did not observe any difference in neutrophil survival when co-cultured with low-metastatic L3.3 cell. However, neutrophil survival was significantly reduced when co-cultured with L3.6 cells (high metastatic). Together, our data suggest that PDAC-neutrophil interaction differentially modulates of neutrophil and PDAC cells survival/proliferation.
Metastasis, Pancreatic Ductal Adenocarcinoma, Neutrophils, PDAC-neutrophil interaction, proliferation, survival
Maher, Michael; Sturgeon, Reegan; Abrahams, Lauren; Tinsley, Parker; Johnson, Esther; and Singh, Rakesh, "Metastatic PDAC Cell – Neutrophil Interaction Regulates their Proliferation and Survival" (2023). Posters: 2023 Summer Undergraduate Research Program. 14.