Abstract
During chemotherapy, structural and mechanical changes in malignant cells have been observed in several cancers, including leukaemia, pancreatic and prostate cancer. Such cellular changes may act as physical biomarkers for chemoresistance and cancer recurrence. This study aimed to determine how exposure to paclitaxel affects the intracellular stiffness of human oesophageal cancer of South African origin in vitro. A human oesophageal squamous cell carcinoma cell line WHCO1 was cultured on glass substrates (2D) and in collagen gels (3D) and exposed to paclitaxel for up to 48 hours. Cellular morphology and stiffness were assessed with confocal microscopy, visually aided morpho-phenotyping image recognition, and mitochondrial particle tracking microrheology at 24 and 48 hours. In the 2D environment, the intracellular stiffness was higher for the paclitaxel-treated than for untreated cells at 24 and 48 hours. In the 3D environment, the paclitaxel-treated cells were stiffer than the untreated cells at 24 hours, but no statistically significant differences in stiffness were observed at 48 hours. In 2D, paclitaxel-treated cells were significantly larger at 24 and 48 hours and more circular at 24 but not at 48 hours than the untreated controls. In 3D, there were no significant morphological differences between treated and untreated cells. The shape heterogeneity was lower for paclitaxel-treated than untreated cells in 3D and similar for the treated and untreated groups in 2D. Future studies with patient-derived primary cancer cells and prolonged drug exposure will help identify physical cellular biomarkers to detect chemoresistance onset and assess therapy effectiveness in oesophageal cancer patients.
Insight Mechanical changes in cancer cells brought on by chemotherapeutic drug exposure offer possible physical biomarkers to detect chemoresistance and cancer recurrence. This first study on human oesophageal squamous cell carcinoma of South African origin indicated that in vitro paclitaxel treatment induced stiffening and enlarging of the malignant cells in two-dimensional environments at 24 and 48 hours. In physiologically more relevant three-dimensional collagen matrices, however, the paclitaxel treatment led to cellular stiffening at 24 hours but softening after that, without significant changes in cellular size at any time. The in vitro environment’s influence on experimental outcomes needs to be considered in further studies with prolonged drug exposure and patient-derived primary cancer cells.
Competing Interest Statement
The authors have declared no competing interest.
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