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Fayth L. Miles Biological Sciences Department Cancer Biology Research Laboratory University of Delaware, Newark, DE USA. Prostate Cancer-A Big Problem. The Rose Bowl (~90,000 capacity). ~240,000 new cases/yr. http://www.roadtrips.com/rose-bowl.php 9/5/06. The Prostate. Ribs. Sternum.
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Fayth L. Miles Biological Sciences Department Cancer Biology Research Laboratory University of Delaware, Newark, DE USA
Prostate Cancer-A Big Problem The Rose Bowl (~90,000 capacity) ~240,000 new cases/yr http://www.roadtrips.com/rose-bowl.php 9/5/06
Ribs Sternum Spine (lumbar) Pelvic Girdle Femur Prostate Cancer Metastasizes Preferentially to Bone Normal Diseased
CAMs ROS VEGF SDF-1α Rho GTPases Prostate Cancer (PC) Adhesion to Bone Marrow Endothelial Cells (1) PC “docks” to endothelial cell (EC) (2) PC “Locks” to EC (3) PC migrates through EC CC selectins (TGF-1) EC Retraction/Damage EC selectins EC Adherens junctions -PECAM -VE-cadherin Actin reorganization; opening of EC contacts
Cell Adhesion Assay TGF-β1-treated control labeled-PCa cells BMEC BMEC BMEC BMEC Wash BMEC Quantitate
Adhesion to Bone Marrow Endothelial Cells control 18-hour TGF-β1
CAMs ROS VEGF SDF-1α Rho GTPases (1) Prostate Cancer cell (PC) “docks” to endothelial cell (EC) (2) PC “Locks” to EC (3) PC migrates through EC CC selectins X X EC Retraction/Damage EC selectins X EC Adherens junctions -PECAM -VE-cadherin Actin reorganization; opening of EC contacts
Fluid shear flow loop Media reservoir Pump (Monolayer of cells under a well defined laminar steady fluid shear of 12 dynes/cm2) Chamber ---- From Suzanne Norvell