Abstract
Author(s): Lu, T; Anvari, B | Abstract: Ovarian cancer is the deadliest gynecological cancer in women. It is a highly metastatic disease with pelvis, regional lymph nodes, and peritoneal cavity as major sites for tumor deposits. Mechanical properties of ovarian cancer cells can play a major role in metastasis as the cells detach from the ovaries and undergo deformation during the metastatic process. Herein, we have characterized the viscoelastic properties of the plasma membrane of normal epithelial (IOSE364) and cancerous (SKOV3) ovarian cells by optical tweezers and quantitative phase imaging. Using optical tweezers, we obtained time-resolved force profiles associated with membrane tethers pulled from the cells. We used quantitative phase imaging to measure the diameter of membrane tethers, and subsequently, estimated the membrane bending modulus and membrane tension in the tether. Our results indicate that the force (190 ± 76npN) (mean ± standard deviation) required to separate the membrane of SKOV3 cells from the cytoskeleton was significantly lower (p = 0.0004) than the force (350 ± 81npN) for IOSE364 cells. The mean stiffness (2.8 ± 0.8npN/μm) of membrane tethers pulled from SKOV3 cells was significantly lower (p = 0.032) than the value for IOSE 364 cells (3.7 ± 0.8npN/μm). Mean value of the force relaxation characteristic time associated with diffusive flow of lipids was also significantly lower (p = 0.018) for SKOV3 membranes (12.9 ± 6.9ns) as compared to the value for IOSE 364 membranes (20.4 ± 6.2ns). Similarly, the mean value of the membrane bending modulus for SKOV3 cells [(0.51 ± 0.23) × 10–18nJ] was significantly lower (p = 0.007) than the value for IOSE364 cells [(1.29 ± 0.32) × 10–18nJ]. Overall, our results suggest that the membranes of SKOV3 cells are less resistant to mechanical deformation. Increased membrane susceptibility to mechanical deformation may be a facilitating factor in the metastatic behavior of cancerous ovarian cells. Characterization of membrane biomechanics may provide a useful diagnostic biomarker for assessment of the metastatic potential of ovarian cancer, and a target for development of therapeutics.
Highlights
Ovarian cancer is one of the deadliest cancers in women with estimated 22,000 new cases and approximately 14,1000 deaths in 2020 [1]
A video of a tether pulling process from an SKOV3 cells is provided in Supplementary Video S1
Both normal and cancerous ovarian cells exhibit similar profiles. These profiles are consistent with those associated with tethers pulled from other cell types, including guinea pig outer hair cells (OHCs) [25], human embryonic kidney (HEK) cells [22], and mouse microglial cells [26]
Summary
Ovarian cancer is one of the deadliest cancers in women with estimated 22,000 new cases and approximately 14,1000 deaths in 2020 [1]. Metastasis is a key determinant in survivability of patients with ovarian cancer. Passive dissemination and hematogenous metastasis are considered as the main mechanisms for ovarian cancer metastasis [3]. Cancer cells detach from the ovaries, and are carried by peritoneal fluid and ascites, reaching the pelvis and peritoneal cavity [4, 5]. Ovarian cancer cells at the primary site invade through the basal membrane of the blood or lymphatic vessels to intravasate into the circulation. Cancer cells extravasate out of the circulation at the metastatic site [3]. Under either of the two mechanisms, the mechanical properties of the cell are the key determinants of its deformability during the detachment, intravasation, and extravasation processes that result in metastasis
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