Veiseh, M. et al. Proc. Natl. Acad. Sci. USA 111, e1731–e1739 (2014).

Tumors are known to be heterogeneous at the genomic and protein levels. Veiseh et al. took heterogeneity profiling a step further, using fluorescent hyaluronic acid (HA), a glycan, to identify stable subpopulations within triple-negative breast cancer cell lines. HA binding to the cells is heterogeneous, and although the overall binding levels correlate with those of the HA receptors CD44 and RHAMM, this heterogeneity cannot be entirely explained by receptor expression level. The researchers made use of the heterogeneous HA signal to sort subpopulations of cells by flow cytometry. The subpopulations were stable and phenotypically different in both in vitro and in vivo assays: cells with high HA binding proliferated more slowly but appeared to be more invasive in three-dimensional cultures than cells with low HA binding. Sugar profiling thus uncovers or stabilizes previously unknown functional heterogeneity in even well-studied tumor cell lines.