Transcript Fayth L. Miles Biological Sciences Department Cancer Biology Research Laboratory University of Delaware, Newark, DE USA.

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)
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~240,000 new
cases/yr
http://www.roadtrips.com/rose-bowl.php 9/5/06
The Prostate
Prostate Cancer Metastasizes
Preferentially to Bone
Sternum
Ribs
Spine (lumbar)
Pelvic Girdle
Femur
Normal
Diseased
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
CAMs
EC Adherens junctions
-PECAM
-VE-cadherin
Rho GTPases
Actin
reorganization;
opening of EC
contacts
ROS
VEGF
SDF-1α
Cell Adhesion Assay
TGF-β1-treated
control
labeled-PCa cells
BMEC
BMEC
BMEC
BMEC
Wash
Quantitate
BMEC
Adhesion to Bone Marrow Endothelial Cells
control
18-hour TGF-β1
(1) Prostate Cancer cell
(PC) “docks” to
endothelial cell (EC)
(2) PC “Locks” to EC
(3) PC migrates through EC
CC selectins
EC selectins
X
CAMs
EC Adherens junctions
-PECAM
-VE-cadherin
EC Retraction/Damage
X
Rho GTPases
Actin
reorganization;
opening of EC
contacts
ROS
VEGF
SDF-1α
X
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