Circulating Horizontal Flow Bioreactor Using Tissue Engineering Scaffolds for Evaluating Prostate Cancer Metastasis...

Area of Science:

• Oncology
• Biotechnology
• Cell Biology

Background:

• Prostate cancer mortality is linked to bone metastasis.
• Metastasis involves epithelial to mesenchymal transition (EMT) and mesenchymal to epithelial transition (MET).
• Hypoxia and interstitial fluid flow are key factors in cancer cell migration.

Purpose of the Study:

• To fabricate a bioreactor for recapitulating prostate cancer cell EMT/MET cascade.
• To evaluate the migration of hypoxic prostate cancer cells to bone under fluid flow.
• To understand the role of hypoxia, integrins, and fluid flow in prostate cancer metastasis.

Main Methods:

• Fabrication of a novel bioreactor with an injection port.
• Assessment of αVβ3 integrin activation under hypoxia.
• Evaluation of MET biomarkers (vimentin, E-cadherin) and angiogenic markers (VEGF, MMP-9, FAK) expression.
• Recapitulation of cell migration using hanging drop spheroids and analysis of cell-fibroblast crosstalk.

Main Results:

• Hypoxia activates αVβ3 integrins, enhancing cell attachment and growth.
• Interstitial fluid flow influences the expression of αVβ3, E-cadherin, VEGF, MMP-9, and FAK.
• Hypoxic PC3 cells show increased expression of angiogenic markers.
• Distinct migratory patterns were observed, and cell-fibroblast crosstalk affects spheroid angiogenicity.

Conclusions:

• The developed bioreactor effectively mimics prostate cancer bone metastasis under interstitial fluid flow.
• Understanding these migratory patterns can improve prediction of cancer progression.
• This research aids in identifying therapies for advanced prostate cancer patients.