CHARACTERIZING PANCREATIC CANCER SIGNALING, TOPOGRAPHY, AND CHEMOTHERAPEUTIC OUTCOMES WITH ORGANOID AND LIGHT-SHEET MICROSCOPIC THREE-DIMENSIONAL MODELS
Pancreatic cancer has a 5-year survival of just 10%, in part because it is aggressively invasive. Three-dimensional organoid cell cultures provide a way to investigate this invasion because they derive directly from patient tumors and maintain complex cellular interactions. Cancer-associated fibroblasts (CAFs) are the body’s own cells that surround and influence cancers, often by producing extracellular signals. These experiments studied the interaction between CAFs and pancreatic cancer organoids and the impact of CAF signals on cancer invasion. Tumors were digested; cancer cells and CAFs from each tumor were sorted and cultured separately. After growing for 72 hours, CAFs were filtered out of their media, leaving only extracellular signals behind. CAF media was added to gels containing organoids derived from either the same patient or, most of the time, a different patient. Image analysis of the organoids was performed, and the circularity (roundness) of each image was traced with a Fiji picture-analysis system. While adding CAF media only slightly increased the percentage of invasive organoids, it significantly increased (p<0.05) the degree of invasiveness, as measured by the inverse of circularity. Importantly, this increased invasiveness was independent of whether the CAFs and cancers derived from the same patient or different patients. These data show that CAFs provide important, patient-independent extracellular signals influencing the invasiveness of pancreatic cancer. We now also have begun to build a database of three-dimensional computer images of resected pancreatic cancers derived from both control tumors and tumors treated with chemotherapy. Our expanding database of tumor images will be used to further understand the effects of chemotherapy on cancer shape and growth and specify areas of invasion for genetic study with the goal of developing treatments to block local and metastatic cancer spread.
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Daniel Wilentz is currently a senior at Pine Crest School and next year will attend Harvard College. As a member of Pine Crest’s Science Research Program, Daniel has investigated pancreatic cancer invasion at Johns Hopkins School of Medicine, and he hopes one day to apply his findings to help treat and cure cancer. In addition, Daniel is a member of the Family Toolkit Committee for the National Pediatric Cancer Foundation and a co-founder of the Teen Ambassadors of The Childhood Cancer Project. Outside of science, Daniel hopes to increase understanding among people of different faiths as a leader in his school’s Interfaith Dialogue Club, the South Florida community’s JAM and ALL Interfaith Youth Board, and the International Interfaith Council for Young Adults. Daniel also tutors and serves as a camp counselor for Love Our Nation youth empowerment group and loves playing percussion in his high school’s concert and jazz bands.