Carcinomas with Occult Metastasis Potential: Diagnosis/Prognosis Accuracy Improvement by Means of Force Spectroscopy

Abstract

Accurate diagnosis of cancer stage is inevitable for the following prognosis in patients struggling with these lesions to promote their health and survival rate. Previous studies on survival rate statistics show, in some cases, failure in cancer stage surveys in which metastasis or recurrence of the disease was not accurately prognosed. Morphology study of cancer cells advances the understanding about cancer behavior and its progression, in which, in our previous study on invasive cancer cells, fewer formations of cytoskeleton components compared to their counterparts was observed. Here it is shown that carcinomas with an occult propensity of metastasis depict a number of poorly differentiated cells with decreased amounts of cytoskeleton components in a near‐well differentiated population. Force spectroscopy in conjunction with fluorescence microscopy of lung cancer, liver hepatoma, and melanoma provides a general view of these cells’ architecture, leading to the conclusion that the scarce abnormal‐shaped cells with low formation of structural filaments convey the high risk of metastatic potential of the tumor. The results demonstrate that force spectroscopy complements conventional diagnostic approaches by an accurate cytoskeleton assessment and can improve the following prognosis in epithelial cancers with occult metastasis risk.

The cyto-linker and scaffolding protein “plectin” mis-localization leads to softening of cancer cells

“…This agrees with the findings that the cytoskeleton, specifically the MTs network, does not provide a good shield against an external force on top of the cancer cell's nucleus. 46,47 In addition, cancer cell nuclei isolated from the carcinoma cells show lower elasticity compared to healthy mammary cells, with median values of 21.76 kPa (MAD = 13.25 kPa) and 38.10 kPa (MAD = 27.85 kPa), respectively (20 nuclei were measured from each cell line, and the stiffness distribution and statistics of the measured nuclei are given in ESI Fig. S5c †).…”

“…We have shown several epithelial cancer cell lines (invasive ductal carcinoma BT20 cell line, amelanotic melanoma HS695T cell line, liver hepatoma PLC/PRF/5 cell line, and human lung cancer Calu_1 cell line) presenting cytoskeletal distortion while indicating lower stiffness compared to their healthy counterparts 46 or well-differentiated cancer cells. 47,48 In these studies, based on the quantitative nano-mechanical characterization in PeakForce-tapping (PFT-QNM) AFM mode, images of cancerous cells showed scarce cytoskeletal filaments on the cells in direct comparison with the healthy cells. According to the conformational indications, we attributed the lower bending rigidity of cancer cells predominantly to lesser microtubule assembly.…”