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Cell stiffness is a biomarker of the metastatic potential of ovarian cancer cells.

ABSTRACT: The metastatic potential of cells is an important parameter in the design of optimal strategies for the personalized treatment of cancer. Using atomic force microscopy (AFM), we show, consistent with previous studies conducted in other types of epithelial cancer, that ovarian cancer cells are generally softer and display lower intrinsic variability in cell stiffness than non-malignant ovarian epithelial cells. A detailed examination of highly invasive ovarian cancer cells (HEY A8) relative to their less invasive parental cells (HEY), demonstrates that deformability is also an accurate biomarker of metastatic potential. Comparative gene expression analyses indicate that the reduced stiffness of highly metastatic HEY A8 cells is associated with actin cytoskeleton remodeling and microscopic examination of actin fiber structure in these cell lines is consistent with this prediction. Our results indicate that cell stiffness may be a useful biomarker to evaluate the relative metastatic potential of ovarian and perhaps other types of cancer cells.

SUBMITTER: Xu W

PROVIDER: S-EPMC3464294 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Cell stiffness is a biomarker of the metastatic potential of ovarian cancer cells.

Xu Wenwei W Mezencev Roman R Kim Byungkyu B Wang Lijuan L McDonald John J Sulchek Todd T

PloS one 20121004 10

The metastatic potential of cells is an important parameter in the design of optimal strategies for the personalized treatment of cancer. Using atomic force microscopy (AFM), we show, consistent with previous studies conducted in other types of epithelial cancer, that ovarian cancer cells are generally softer and display lower intrinsic variability in cell stiffness than non-malignant ovarian epithelial cells. A detailed examination of highly invasive ovarian cancer cells (HEY A8) relative to th ...[more]

PMID: 23056368

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Project description:High metastatic potential and resistance to immunotherapy lead to poor survival in patients with ovarian cancer. Angiopoietin-like protein 3 is aberrantly expressed and exerts diverse roles in the progression of several cancers. However, its function in ovarian cancer is unknown. Here, decreased expression of angiopoietin-like protein 3 was observed in ovarian cancer tissues and cells. Moreover, patients with high expression of angiopoietin-like protein 3 had longer overall survival and progression-free survival, indicating a good prognosis for patients. Furthermore, angiopoietin-like protein 3 overexpression inhibited ovarian cancer cell proliferation. Concomitantly, high invasion and the occurrence of epithelial-to-mesenchymal transition of cancer cells were restrained after angiopoietin-like protein 3 elevation. Up-regulation of angiopoietin-like protein 3 expression further increased interleukin 2-treated natural killer cell activation by increasing CD69 expression and production of interferon gamma and tumor necrosis factor-alpha when natural killer cells were co-cultured with ovarian cancer cells. Importantly, angiopoietin-like protein 3 overexpression enhanced natural killer cell-evoked cytotoxicity and apoptosis of cancer cells, indicating the pro-tumor killing ability of angiopoietin-like protein 3 for natural killer cells. Mechanistically, angiopoietin-like protein 3 elevation inhibited activation of the Janus Kinase/Signal transducer and activator of transcription 3 signaling in ovarian cancer cells by inhibiting protein expression of phospho-Janus Kinase 2, phospho-Signal transducer and activator of transcription 3, downstream matrix metallopeptidase 2 and programmed cell death 1. Moreover, blocking the Janus Kinase/Signal transducer and activator of transcription 3 pathway via their inhibitor Stattic restrained ovarian cancer cell proliferation, invasion, epithelial-to-mesenchymal transition, and promoted natural killer cell killing to ovarian cancer cells. Thus, these findings reveal that angiopoietin-like protein 3 may act as an anti-oncogenic regulator to inhibit the metastatic potential and enhance the susceptibility of ovarian cancer cells to natural killer cell-mediated killing. Consequently, angiopoietin-like protein 3 may regulate metastatic potential and immune escape from natural killer cells, indicating a promising therapeutic strategy for ovarian cancer.

Dataset Information

Cell stiffness is a biomarker of the metastatic potential of ovarian cancer cells.

Publications

Cell stiffness is a biomarker of the metastatic potential of ovarian cancer cells.

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