Biomechanical profiles and molecular regulation of clinical cancer stem cells and tumor cells: Implications for tumorigenicity and metastasis of lung cancer

The biomechanics of clinical cancer stem cells (CSCs) and tumor cells (TCs) play a crucial role in cancer progression. We compared the biomechanical profiles of clinical CSCs and TCs from untreated patients with lung benign (LB) and malignant (LM) tumors, including lung adenocarcinoma (LADC) and lung squamous cell carcinoma (LSCC). The results showed that TCs were mechanically stiffer than CSCs, with a greater stiffness increase in LB tumors compared to LM tumors., indicating that LB tumors have softer CSCs and stiffer TCs than those of LM tumors. The mechanical properties of TCs and CSCs from individual patients were linearly correlated for each tumor type and may be related to the tumor stage and grade. These findings align with cytoskeletal and morphological analyses of CSCs and TCs. Furthermore, we identified genes and proteins, such as BCL9L, that regulate cellular mechanical properties and explain the changes in these characteristics during differentiation from CSCs to TCs. Finally, the joint mechanical properties of CSCs and TCs serve as better biomarkers than the mechanical properties of either CSCs or TCs for tumor classification. STATEMENT OF SIGNIFICANCE: The biomechanics of clinical cancer stem cells (CSCs) and tumor cells (TCs) play a pivotal role in cancer progression. This study demonstrates that TCs exhibit greater stiffness compared to CSCs, with notable distinctions observed between benign and malignant lung tumors. The mechanical properties of CSCs and TCs are strongly correlated with tumor type, stage, and grade, while regulatory genes such as BCL9L contribute to these biomechanical variations. Importantly, the combined biomechanical profiles of CSCs and TCs outperform the individual properties of either cell type as biomarkers for tumor classification.