(239h) Cooperation Between Subtypes of Tumor Cells Promotes Malignancy Studied by Multiplexed Super-Resolution Single Cell Proteomic Assay

Glioblastoma multiforme (GBM) is the most common and malignant brain cancer in adult. Amplification of epidermal growth factor receptor (EGFR) expression has been found in ~50% of primary GBMs, and associated with poor prognosis. The EGFR variant, EGFRvIII, represents the most common mutant and persistently activates cancer cells to be highly diffusive.  Xenograft assay reveals that, although EGFRvIII⁺ cancer cells grow much faster than EGFRvIII^- cells in vitro, those two cell subtypes proliferate in a manner similar to symbiosis in vivo. Using our single cell barcode chip, we captured both secreted proteins and intracellular phosphoproteins at the single cell level when two cells of different phenotypes were cultured in an artificial microenvironment. Our technology enables quantification of >8 proteins of a single cell with a resolution of ~50 proteins per cell, and gathers information from ~1000 cell pairs. Using information theory and Le Chatelier’s principle, the interaction between cell pairs is predicted, which also explains the activation of EGFRvIII^- cells and fast proliferation in tumor. We construct a model in statistic mechanics to simulate cell subtype composition in a tumor. We further investigate the interaction of EGFRvIII^+/- cells and stromal cells as well as immune cells in our microplatform. The understanding of tumor-host cell interaction will give insight into the tumor heterogeneity and complicated tumor social network.