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The Role of Cancer Stem Cells and Mechanical Forces in Ovarian Cancer Metastasis

1
Department of Biomedical Engineering; University of Michigan, Ann Arbor, MI 48109, USA
2
Department of Materials Science and Engineering; University of Michigan, Ann Arbor, MI 48109, USA
3
Macromolecular Science and Engineering; University of Michigan, Ann Arbor, MI 48109, USA
4
Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2019, 11(7), 1008; https://doi.org/10.3390/cancers11071008
Received: 10 June 2019 / Revised: 12 July 2019 / Accepted: 17 July 2019 / Published: 18 July 2019
(This article belongs to the Special Issue Ovarian Cancer Metastasis)
Ovarian cancer is an extremely lethal gynecologic disease; with the high-grade serous subtype predominantly associated with poor survival rates. Lack of early diagnostic biomarkers and prevalence of post-treatment recurrence, present substantial challenges in treating ovarian cancers. These cancers are also characterized by a high degree of heterogeneity and protracted metastasis, further complicating treatment. Within the ovarian tumor microenvironment, cancer stem-like cells and mechanical stimuli are two underappreciated key elements that play a crucial role in facilitating these outcomes. In this review article, we highlight their roles in modulating ovarian cancer metastasis. Specifically, we outline the clinical relevance of cancer stem-like cells, and challenges associated with their identification and characterization and summarize the ways in which they modulate ovarian cancer metastasis. Further, we review the mechanical cues in the ovarian tumor microenvironment, including, tension, shear, compression and matrix stiffness, that influence (cancer stem-like cells and) metastasis in ovarian cancers. Lastly, we outline the challenges associated with probing these important modulators of ovarian cancer metastasis and provide suggestions for incorporating these cues in basic biology and translational research focused on metastasis. We conclude that future studies on ovarian cancer metastasis will benefit from the careful consideration of mechanical stimuli and cancer stem cells, ultimately allowing for the development of more effective therapies. View Full-Text
Keywords: ovarian cancer metastasis; cancer stem cells; mechanical stimulation; mechanotransduction; tension; compression; shear stress; viscoelastic; ascites; matrix stiffness ovarian cancer metastasis; cancer stem cells; mechanical stimulation; mechanotransduction; tension; compression; shear stress; viscoelastic; ascites; matrix stiffness
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Bregenzer, M.E.; Horst, E.N.; Mehta, P.; Novak, C.M.; Repetto, T.; Mehta, G. The Role of Cancer Stem Cells and Mechanical Forces in Ovarian Cancer Metastasis. Cancers 2019, 11, 1008.

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