We are among the earliest groups to report cell-heterogeneous expression of 2,6-linked sialic acids (2,6-Sial) in breast cancer cells using lectin cytometry and quantitative mass spectrometry. This heterogeneity is directly linked to differences in ECM adhesion. Using in‑house-designed 3D multi-ECM assays that can dissect collective-, single cell mesenchymal- and multimodal migration morphologies, we observed how 2,6-Sial-driven adhesion heterogeneity was able to sort progenitor invasive cells to the boundary of tumoroids. Cellular Potts-based multiscale simulations showed that the less-adhesive and invasive core and the confining ECM were both crucial to the sorting (Pally et al Front Physiol Biophys, 2019; Pally et al ACS Central Sci, 2021).
In contrast to 2,6-Sial, 2,3-Sial signals were observed to extend beyond cell surfaces around breast tumoroids cultured within laminin-rich ECM. Using charge-sensing nanorobotic probes in collaboration with Prof Ambarish Ghosh’s active matter group (Nanosciences, IISc), we identified ECM zones with novel electrochemical properties that would be used to localize agents to 3D cancer niches; such zones were absent around untransformed acini within the same milieu (Dasgupta, Pally et al Angew Chem, 2020 [top 5% papers based on peer reviews]). My group’s collaboration with Prof Deepak Saini’s and Prof Ambarish Ghosh’s groups (IISc) has used the motility mechanics of magnetically actuatable nanorobots to probe the rheological properties of cancer cell cytoplasm (Pal et al, Adv Mat, 2017) and ECMs (Pal et al, J Phys Cond Matt, 2020).
In addition to sialic acids, commonly part of N-linked glycans, we have reported the invasion-relevant dynamics of O-linked glycosaminoglycans (GAGs), specifically dermatan sulfates (DS): decreased levels of its desulfating enzyme iduronate-2-sulfatase increased DS accumulation, ECM stiffness, Collagen I (Coll I) fibrillar patterning, and invasiveness of breast cancer cells (Singh et al, J Clin Med, 2010, Singh et al, Front Biosci, 2020).
In addition, my group is engaged in studying the morphogenetic capabilities of circulating breast tumor cells (CTCs). This requires their long-term culture within different tumor microenvironments. In collaboration with Prof Prosenjit Sen’s microfluidics group (IISc), we published a fluid physics-based method to isolate cancer cells from a vascular milieu even at challenging low-flow velocities, increasing their amenability for downstream culture applications (Rastogi et al, Anal Chim Acta, 2021).
