| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Department of Chemical Engineering, Johns Hopkins University, Baltimore, MD 21218; and
Department of Medicine, Division of Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, MD 21224
The ability of tumor cells to metastasize hematogenously is regulated by their interactions with polymorphonuclear leukocytes (PMNs). However, the mechanisms mediating PMN binding to tumor cells under physiological shear forces remain largely unknown. This study was designed to characterize the molecular interactions between PMNs and tumor cells as a function of the dynamic shear environment, using two human colon adenocarcinoma cell lines (LS174T and HCT-8) as models. PMN and colon carcinoma cell suspensions, labeled with distinct fluorophores, were sheared in a cone-and-plate rheometer in the presence of the PMN activator fMLP. The size distribution and cellular composition of formed aggregates were determined by flow cytometry. PMN binding to LS174T cells was maximal at 100 s-1 and decreased with increasing shear. At low shear (100 s-1) PMN CD11b alone mediates PMN-LS174T heteroaggregation. However, L-selectin, CD11a, and CD11b are all required for PMN binding to sialyl Lewisx-bearing LS174T cells at high shear (800 s-1). In contrast, sialyl Lewisx-low HCT-8 cells fail to aggregate with PMNs at high shear conditions, despite extensive adhesive interactions at low shear. Taken together, our data suggest that PMN L-selectin initiates LS174T cell tethering at high shear by binding to sialylated moieties on the carcinoma cell surface, whereas the subsequent involvement of CD11a and CD11b converts these transient tethers into stable adhesion. This study demonstrates that the shear environment of the vasculature modulates the dynamics and molecular constituents mediating PMN-tumor cell adhesion.
This article has been cited by other articles:
|
|
 |
|
  S. N. Thomas, R. L. Schnaar, and K. Konstantopoulos Podocalyxin-like protein is an E-/L-selectin ligand on colon carcinoma cells: comparative biochemical properties of selectin ligands in host and tumor cells Am J Physiol Cell Physiol, March 1, 2009; 296(3): C505 - C513. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Liang and C. Dong Integrin VLA-4 enhances sialyl-Lewisx/a-negative melanoma adhesion to and extravasation through the endothelium under low flow conditions Am J Physiol Cell Physiol, September 1, 2008; 295(3): C701 - C707. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. N. Thomas, F. Zhu, R. L. Schnaar, C. S. Alves, and K. Konstantopoulos Carcinoembryonic Antigen and CD44 Variant Isoforms Cooperate to Mediate Colon Carcinoma Cell Adhesion to E- and L-selectin in Shear Flow J. Biol. Chem., June 6, 2008; 283(23): 15647 - 15655. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Alves, M. M. Burdick, S. N. Thomas, P. Pawar, and K. Konstantopoulos The dual role of CD44 as a functional P-selectin ligand and fibrin receptor in colon carcinoma cell adhesion Am J Physiol Cell Physiol, April 1, 2008; 294(4): C907 - C916. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Liang, C. Fu, D. Wagner, H. Guo, D. Zhan, C. Dong, and M. Long Two-dimensional kinetics of {beta}2-integrin and ICAM-1 bindings between neutrophils and melanoma cells in a shear flow Am J Physiol Cell Physiol, March 1, 2008; 294(3): C743 - C753. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. Napier, Z. R. Healy, R. L. Schnaar, and K. Konstantopoulos Selectin Ligand Expression Regulates the Initial Vascular Interactions of Colon Carcinoma Cells: THE ROLES OF CD44V AND ALTERNATIVE SIALOFUCOSYLATED SELECTIN LIGANDS J. Biol. Chem., February 9, 2007; 282(6): 3433 - 3441. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Burdick, J. T. Chu, S. Godar, and R. Sackstein HCELL Is the Major E- and L-selectin Ligand Expressed on LS174T Colon Carcinoma Cells J. Biol. Chem., May 19, 2006; 281(20): 13899 - 13905. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Laubli, J. L. Stevenson, A. Varki, N. M. Varki, and L. Borsig L-Selectin Facilitation of Metastasis Involves Temporal Induction of Fut7-Dependent Ligands at Sites of Tumor Cell Arrest Cancer Res., February 1, 2006; 66(3): 1536 - 1542. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Panorchan, M. S. Thompson, K. J. Davis, Y. Tseng, K. Konstantopoulos, and D. Wirtz Single-molecule analysis of cadherin-mediated cell-cell adhesion J. Cell Sci., January 1, 2006; 119(1): 66 - 74. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Slattery, S. Liang, and C. Dong Distinct role of hydrodynamic shear in leukocyte-facilitated tumor cell extravasation Am J Physiol Cell Physiol, April 1, 2005; 288(4): C831 - C839. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Burdick and K. Konstantopoulos Platelet-induced enhancement of LS174T colon carcinoma and THP-1 monocytoid cell adhesion to vascular endothelium under flow Am J Physiol Cell Physiol, August 1, 2004; 287(2): C539 - C547. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Pawar, P. K. Shin, S. A. Mousa, J. M. Ross, and K. Konstantopoulos Fluid Shear Regulates the Kinetics and Receptor Specificity of Staphylococcus aureus Binding to Activated Platelets J. Immunol., July 15, 2004; 173(2): 1258 - 1265. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. D. Hanley, D. Wirtz, and K. Konstantopoulos Distinct kinetic and mechanical properties govern selectin-leukocyte interactions J. Cell Sci., May 15, 2004; 117(12): 2503 - 2511. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. K. HSIAI, S. K. CHO, P. K. WONG, M. ING, A. SALAZAR, A. SEVANIAN, M. NAVAB, L. L. DEMER, and C.-M. HO Monocyte recruitment to endothelial cells in response to oscillatory shear stress FASEB J, September 1, 2003; 17(12): 1648 - 1657. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. J. T. McCarty, N. Tien, B. S. Bochner, and K. Konstantopoulos Exogenous eosinophil activation converts PSGL-1-dependent binding to CD18-dependent stable adhesion to platelets in shear flow Am J Physiol Cell Physiol, May 1, 2003; 284(5): C1223 - C1234. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Burdick, J. M. McCaffery, Y. S. Kim, B. S. Bochner, and K. Konstantopoulos Colon carcinoma cell glycolipids, integrins, and other glycoproteins mediate adhesion to HUVECs under flow Am J Physiol Cell Physiol, April 1, 2003; 284(4): C977 - C987. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Hanley, O. McCarty, S. Jadhav, Y. Tseng, D. Wirtz, and K. Konstantopoulos Single Molecule Characterization of P-selectin/Ligand Binding J. Biol. Chem., March 14, 2003; 278(12): 10556 - 10561. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Jadhav and K. Konstantopoulos Fluid shear- and time-dependent modulation of molecular interactions between PMNs and colon carcinomas Am J Physiol Cell Physiol, October 1, 2002; 283(4): C1133 - C1143. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
