Tumor Cell - Vascular Cell Interactions In Shear Flow:
Blood-borne
metastasis is a highly regulated and dynamic process in which
cancerous cells separate from a primary tumor, migrate across blood vessel walls into the
bloodstream, and disperse throughout the body to generate new colonies. During
their transit into the circulatory system, tumor cells are exposed to fluid
mechanical forces, plasma proteins, and vascular cells such as platelets and
neutrophils, all of which may affect their survival and extravasation from the
vasculature.
All previous in vitro experimental models used for the study of tumor
cell-vascular cell interactions were based on static conditions, which neglect
the rheological parameters of fluid flow in the vasculature. As has been
extensively argued in the literature, data obtained in vitro using static
binding assays may not be relevant to the fluid mechanic conditions present in
vivo. Consequently the goal of our research is to systematically and
comprehensively characterize the effects of fluid mechanical stresses on tumor
cell-vascular cell interactions at the molecular level.
Select Publications:
S.L. Napier, Z.R. Healy, R.L. Schnaar,
K. Konstantopoulos, "Selectin Ligand Expression Regulates the Initial Vascular Interactions of Colon Carcinoma Cells: The Roles of CD44v and Alternate Sialofucosylated Selectin Ligands",
Journal of Biological Chemistry 282(6); 3433-3441, 2007.
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W.D. Hanley, S. Napier, M.M. Burdick, R.L. Schnaar, R. Sackstein,
K. Konstantopoulos, "Variant CD44 Isoforms are the P- and L- Selectin Ligands on Colon Carcinomas".
The FASEB Journal. Published electronically 2005 Dec 13.
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W.D. Hanley, M.M. Burdick,
K. Konstantopoulos, and R. Sackstein, "CD44 on LS174T Colon Carcinoma Cells Possesses E-Selectin Ligand Activity."
Cancer Research.
65(13);5812-7, 2005.
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M.M. Burdick and
K. Konstantopoulos,
“Platelet-Induced Enhancement of Colon Carcinoma Cell Adhesion to Vascular
Endothelium Under Flow”,
American
Journal of Physiology Cell Physiology 287(2);
C539-C547, 2004.
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M.M. Burdick, J.M. McCaffery, Y.S. Kim, B.S. Bochner,
K. Konstantopoulos,
“Colon Carcinoma Cell Glycolipids, Integrins, and other Glycoproteins Mediate
Adhesion to HUVECs Under Flow”,
American
Journal of Physiology Cell Physiology 284(4);
C977-C987, 2003.
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W.D. Hanley, O.J.-T. McCarty, S. Jadhav, Y. Tseng, D. Wirtz, and
K.
Konstantopoulos, “Single-Molecule Characterization of P-selectin/Ligand
Binding”
Journal of Biological Chemistry 278(12); 10556-10661, 2003.
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S. Jadhav and
K. Konstantopoulos, “Fluid Shear- and Time-Dependent
Modulation of Molecular Interactions Between Polymorphonuclear Leukocytes and
Colon Carcinomas”,
American Journal of
Physiology Cell Physiology,
283(4); C1133-C1143,
2002.
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O.J.T. McCarty, S. Jadhav, M.M. Burdick, W.R. Bell,
K. Konstantopoulos,
“Fluid Shear Regulates the Kinetics and Molecular Mechanisms of
Activation-Dependent Platelet Binding to Colon Carcinoma Cells”,
Biophysical
Journal 83(8); 836-848, 2002.
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S. Jadhav, B.S. Bochner,
K. Konstantopoulos, “Hydrodynamic Shear
Regulates the Kinetics and Receptor Specificity of Polymorphonuclear
Leukocyte-Colon Carcinoma Cell Adhesive Interactions”,
Journal
of Immunology 167(10); 5986-5993,
2001.
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M.M. Burdick, O.J.T. McCarty, S. Jadhav,
K. Konstantopoulos, “Cell-Cell
Interactions in Inflammation and Cancer Metastasis”
IEEE
Engineering in Medicine and Biology 20(3);
86-91, 2001.
O.J.T. McCarty, S.A. Mousa, P.F. Bray,
K. Konstantopoulos, “Immobilized
Platelets Support Human Colon Carcinoma Cell Tethering, Rolling and Firm
Adhesion Under Dynamic Flow Conditions”,
BLOOD
96(5); 1789-1797,
2000.
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