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Abstract During the migration of cancer cells for metastasis, cancer cells can be exposed to fluid shear conditions. We examined two breast cancer cell lines, MDA-MB-468 (less metastatic) and MDA-MB-231 (more metastatic), and a benign MCF-10A epithelial cell line for their responsiveness in migration to fluid shear. We tested fluid shear at 15 dyne/cm2 that can be encountered during breast cancer cells traveling through blood vessels or metastasizing to mechanically active tissues such as bone. MCF-10A exhibited the least migration with a trend of migrating in the flow direction. Intriguingly, fluid shear played a potent role as a trigger for MDA-MB-231 cell migration, inducing directional migration along the flow with significantly increased displacement length and migration speed and decreased arrest coefficient relative to unflowed MDA-MB-231. In contrast, MDA-MB-468 cells were markedly less migratory than MDA-MB-231 cells, and responded very poorly to fluid shear. As a result, MDA-MB-468 cells did not exhibit noticeable difference in migration between static and flow conditions, as was distinct in root-mean-square (RMS) displacement—an ensemble average of all participating cells. These may suggest that the difference between more metastatic MDA-MB-231 and less metastatic MDA-MB-468 breast cancer cells could be at least partly involved with their differential responsiveness to fluid shear stimulatory cues. Our study provides new data in regard to potential crosstalk between fluid shear and metastatic potential in mediating breast cancer cell migration.
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Interstitial fluid flow contributes to prostate cancer invasion and migration to bone; study conducted using a novel horizontal flow bioreactor
Abstract Prostate cancer bone metastasis is the leading cause of cancer-related mortality in men in the United States, causing severe damage to skeletal tissue. The treatment of advanced-stage prostate cancer is always challenging due to limited drug treatment options, resulting in low survival rates. There is a scarcity of knowledge regarding the mechanisms associated with the effects of biomechanical cues by the interstitial fluid flow on prostate cancer cell growth and migration. We have designed a novel bioreactor system to demonstrate the impact of interstitial fluid flow on the migration of prostate cancer cells to the bone during extravasation. First, we demonstrated that a high flow rate induces apoptosis in PC3 cells via TGF-β1 mediated signaling; thus, physiological flow rate conditions are optimum for cell growth. Next, to understand the role of interstitial fluid flow in prostate cancer migration, we evaluated the migration rate of cells under static and dynamic conditions in the presence or absence of bone. We report that CXCR4 levels were not significantly changed under static and dynamic conditions, indicating that CXCR4 activation in PC3 cells is not influenced by flow conditions but by the bone, where CXCR4 levels were upregulated. The bone-upregulated CXCR4 levels led to increased MMP-9 levels resulting in a high migration rate in the presence of bone. In addition, upregulated levels ofαvβ3integrins under fluid flow conditions contributed to an overall increase in the migration rate of PC3 cells. Overall, this study demonstrates the potential role of interstitial fluid flow in prostate cancer invasion. Understanding the critical role of interstitial fluid flow in promoting prostate cancer cell progression will enhance current therapies for advanced-stage prostate cancer and provide improved treatment options for patients.
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- Award ID(s):
- 1946202
- PAR ID:
- 10402024
- Publisher / Repository:
- IOP Publishing
- Date Published:
- Journal Name:
- Biofabrication
- Volume:
- 15
- Issue:
- 2
- ISSN:
- 1758-5082
- Page Range / eLocation ID:
- Article No. 025017
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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