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Effect of paclitaxel treatment on cellular mechanics and morphology of human oesophageal squamous cell carcinoma in 2D and 3D environments

Effect of paclitaxel treatment on cellular mechanics and morphology of human oesophageal squamous cell carcinoma in 2D and 3D environments
Effect of paclitaxel treatment on cellular mechanics and morphology of human oesophageal squamous cell carcinoma in 2D and 3D environments
During chemotherapy, structural and mechanical changes in malignant cells have been observed in several cancers, including leukaemia and 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 h. Cellular morphology and stiffness were assessed with confocal microscopy, visually aided morpho-phenotyping image recognition and mitochondrial particle tracking microrheology at 24 and 48 h. In the 2D environment, the intracellular stiffness was higher for the paclitaxel-treated than for untreated cells at 24 and 48 h. In the 3D environment, the paclitaxel-treated cells were stiffer than the untreated cells at 24 h, but no statistically significant differences in stiffness were observed at 48 h. In 2D, paclitaxel-treated cells were significantly larger at 24 and 48 h and more circular at 24 but not at 48 h than the untreated controls. In 3D, there were no significant morphological differences between treated and untreated cells. The distribution of cell shapes was not significantly different across the different treatment conditions in 2D and 3D environments. 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.
oesophageal cancer, chemotherapy, chemoresistance, physical biomarker, mechanobiology, collagen, mitochondrial particle tracking microrheology, image recognition
1757-9708
137-149
Kiwanuka, Martin
10eb60a4-4192-4f90-a515-6d0fe83ea8cb
Higgins, Ghodeejah
3aff2432-67fe-41a9-a318-fdcc231991eb
Ngcobo, Silindile
93add4b8-c869-4949-b706-fbd3d445e463
Nagawa, Juliet
a04661e3-a69b-4268-9432-2d401da2fc3f
Lang, Dirk M.
39c27908-c7f0-42ff-9814-24581bb67ffb
Zaman, Muhammad H.
5e7dd867-cb93-40fb-bb84-ff0f32497487
Davies, Neil H.
e52928b5-b051-443d-87c5-6463fe942865
Franz, Thomas
31f508f4-6851-4274-b256-cc01ab321d50
Kiwanuka, Martin
10eb60a4-4192-4f90-a515-6d0fe83ea8cb
Higgins, Ghodeejah
3aff2432-67fe-41a9-a318-fdcc231991eb
Ngcobo, Silindile
93add4b8-c869-4949-b706-fbd3d445e463
Nagawa, Juliet
a04661e3-a69b-4268-9432-2d401da2fc3f
Lang, Dirk M.
39c27908-c7f0-42ff-9814-24581bb67ffb
Zaman, Muhammad H.
5e7dd867-cb93-40fb-bb84-ff0f32497487
Davies, Neil H.
e52928b5-b051-443d-87c5-6463fe942865
Franz, Thomas
31f508f4-6851-4274-b256-cc01ab321d50

Kiwanuka, Martin, Higgins, Ghodeejah, Ngcobo, Silindile, Nagawa, Juliet, Lang, Dirk M., Zaman, Muhammad H., Davies, Neil H. and Franz, Thomas (2022) Effect of paclitaxel treatment on cellular mechanics and morphology of human oesophageal squamous cell carcinoma in 2D and 3D environments. Integrative Biology, 14 (6), 137-149. (doi:10.1093/intbio/zyac013).

Record type: Article

Abstract

During chemotherapy, structural and mechanical changes in malignant cells have been observed in several cancers, including leukaemia and 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 h. Cellular morphology and stiffness were assessed with confocal microscopy, visually aided morpho-phenotyping image recognition and mitochondrial particle tracking microrheology at 24 and 48 h. In the 2D environment, the intracellular stiffness was higher for the paclitaxel-treated than for untreated cells at 24 and 48 h. In the 3D environment, the paclitaxel-treated cells were stiffer than the untreated cells at 24 h, but no statistically significant differences in stiffness were observed at 48 h. In 2D, paclitaxel-treated cells were significantly larger at 24 and 48 h and more circular at 24 but not at 48 h than the untreated controls. In 3D, there were no significant morphological differences between treated and untreated cells. The distribution of cell shapes was not significantly different across the different treatment conditions in 2D and 3D environments. 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.

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Accepted/In Press date: 10 September 2022
e-pub ahead of print date: 15 October 2022
Keywords: oesophageal cancer, chemotherapy, chemoresistance, physical biomarker, mechanobiology, collagen, mitochondrial particle tracking microrheology, image recognition

Identifiers

Local EPrints ID: 484637
URI: http://eprints.soton.ac.uk/id/eprint/484637
ISSN: 1757-9708
PURE UUID: 3ed68227-b536-4ba7-89d0-33bd7ca95b29

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Date deposited: 17 Nov 2023 18:12
Last modified: 17 Nov 2023 18:12

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Contributors

Author: Martin Kiwanuka
Author: Ghodeejah Higgins
Author: Silindile Ngcobo
Author: Juliet Nagawa
Author: Dirk M. Lang
Author: Muhammad H. Zaman
Author: Neil H. Davies
Author: Thomas Franz

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