Abstract: Characterization of Heterogeneous Human Colon Carcinoma Cells Using 2D and 3D Tissue Models (2011 SACNAS National Conference)

Friday, October 28, 2011

Hall 1-2 (San Jose Convention Center)

Alice Martinic , Department of Chemical and Nuclear Engineering, Center for Biomedical Engineering, The University of New Mexico, Albuquerque, NM

Jacqueline De Lora , Department of Chemical and Nuclear Engineering, Center for Biomedical Engineering, The University of New Mexico, Albuquerque, NM

Monique Gallegos , Department of Chemical and Nuclear Engineering, Center for Biomedical Engineering, The University of New Mexico, Albuquerque, NM

Antoinette Trujillo , Department of Chemical and Nuclear Engineering, Center for Biomedical Engineering, The University of New Mexico, Albuquerque, NM

James Freyer, PhD , Department of Chemical and Nuclear Engineering, Center for Biomedical Engineering, The University of New Mexico, Albuquerque, NM

Metastatic disease originating from colorectal cancer is a leading cause of cancer-related deaths in the United States each year. Mutations in phosphatidylinositol-3-kinase (PI3K), an enzyme critical for growth signaling, occur in 1/3 of colorectal cancers and have been shown to alter metastatic behavior. Due to the difficulty of studying mechanisms behind the effects of PI3K mutation in vivo, we are using the spheroid three-dimensional (3D) tumor model in vitro to investigate the mechanisms linking PI3K mutations to increased metastasis. In initial studies with a human colon carcinoma cell line (DLD1) that stably express green fluorescent protein (GFP), two distinct morphologies were observed and used to select two sublines of tumor cells. In monolayer culture, the “brainy” morphology showed flattened, pseudopodia-like attachments while the “smooth” cells were spherical. Spheroids of the brainy subline developed tortuous tubular structures, while smooth cell spheroids have a compact spherical geometry. Monolayer growth curves reveal that brainy and smooth cells had very similar doubling times of 13 and 12 hours, respectively. Brainy cells grew faster as spheroids than smooth cells, with growth rates of 109 µm/day and 77 µm/day, respectively. Cells maintained stable GFP expression under all culture conditions, even to spheroid diameters >2 mm. We plan to use the spheroid cultures of these morphological distinct cell lines to further investigate the mechanisms by which PI3K mutations alter metastatic spread.