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Wednesday, April 11 • 1:45pm - 2:00pm
SYMPOSIA-16: Life in a microsphere: Landscape patterns and competition between two cancer cell lines grown as 3-D cultures

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AUTHORS: Joel S. Brown1,2, Audrey R. Freischel1,2, and Mehdi Damaghi3Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL 1Department of Integrated Mathematical Oncology2Cancer Biology and Evolution Program3Department of Cancer Physiology

ABSTRACT: Tumors are ecosystems populated by normal and cancer cells. Both can exhibit considerable diversity and spatial heterogeneity. Cancer cells vary in their resource uptake, modes of metabolism (glycolytic and acid producing versus more efficient oxidative phosphorylation), motility and susceptibility to the immune system. Distance to vasculature establishes gradients in cell densities and nutrients. Like riparian ecosystems, near blood may lead to denser packing of cancer cells under essentially “mesic” environments. Farther away, cells become less dense and subject to hypoxia, low glucose and acidic conditions (“xeric” environments). To examine competition between cancer cell types, we grew labeled MDA-mb-231 (viewed as highly glycolytic, aggressive, and glucose profligate) and MCF-7 breast cancer cells (viewed as less aggressive but more glucose efficient) in 96 well plates. The former were expected to do best under high glucose and low Ph; the latter under low glucose and normal Ph. Spheroids were established under all combinations of high and no glucose, low and normal Ph, and six different starting ratios. Microspheres were 3-D imaged every 24 hours. Unexpectedly, the MDA-mb-231 outcompeted the MCF-7 under all conditions. Spatially, MDA-mb-231cells were more uniformly distributed throughout the spheroid with highest densities at the outer edge where nutrients will be richest and toxic metabolites lowest. The MCF-7 formed a dense clustered ring inside the microsphere away from both the edge and center. This ring broke up into smaller clusters as they declined in numbers. MCF-7 cells’ need to adhere to each other may disadvantage them from accessing nutrients and from moving to the richer edge of the tumor. Competition assays within the context of landscape ecology permitted a more sophisticated and detailed measure of what makes for “aggressive” and successful cancer cells.

Wednesday April 11, 2018 1:45pm - 2:00pm CDT
Grant Park Parlor

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