Circulating tumor cells (CTCs) mediate hematogenous metastasis and are key targets of liquid biopsy. Although platelet-tumor cell interactions enhance survival and dissemination, systematic studies of CTCs remain limited because of their rarity and heterogeneity. We report a single-cell approach for evaluating platelet-bound CTCs. Platelet binding was induced in urothelial carcinoma cell lines of differing grades (T24, RT112) and quantitatively analyzed using microcavity array (MCA) and three-dimensional (3D) confocal morphometry. In parallel, patient-derived CTCs and platelet-bound CTCs (CTCPLTs) were directly enriched using MCA for identical analyses. Among the tested cell lines, high-grade T24 cells showed higher platelet adhesion, and the bound cells exhibited increased nuclear-to-cytoplasmic (N/C) ratios. In clinical samples, CTCPLTs did not differ from CTCs in terms of N/C ratios or individual morphometric features. Correlation analysis of nuclear and cytoplasmic features (10 representative pairs) revealed enhanced nuclear-cytoplasmic coupling in CTCPLTs, indicating platelet-induced remodeling of the nuclear architecture and coordination. These results demonstrate that single-feature metrics are insufficient for clinical CTCs, whereas correlation-based morphometric analysis provides a sensitive framework for capturing platelet-induced structural plasticity and advancing the phenotypic characterization of CTCs.
Bao et al. (2026) studied this question.