TY - JOUR
T1 - Shear stress and shear rate differentially affect the multi-step process of leukocyte-facilitated melanoma adhesion
AU - Liang, Shile
AU - Slattery, Margaret J.
AU - Dong, Cheng
N1 - Funding Information:
This work was supported by the NIH grant CA-97306, the NSF grant BES-0138474 and in part by the Penn State Biomaterials and Bionanotechnology Summer Institute (NSF-NIH grant EEC-0234026). The GCRC is supported by NIH grants M01-RR-010732 and C06-RR-016499.
PY - 2005/11/1
Y1 - 2005/11/1
N2 - Previous studies have shown that neutrophils (PMNs) facilitate melanoma cell extravasation [M.J. Slattery, C. Dong, Neutrophils influence melanoma adhesion and migration under flow conditions, Intl. J. Cancer 106 (2003) 713-722] Little is known, however, about the specific interactions between PMNs, melanoma and the endothelium (EC) or the molecular mechanism involved under flow conditions. The aim of this study is to investigate a "two-step adhesion" hypothesis that involves initial PMN tethering on the EC and subsequent melanoma cells being captured by tethered PMNs. Different effects of hydrodynamic shear stress and shear rate were analyzed using a parallel-plate flow chamber. Results indicate a novel finding that PMN-facilitated melanoma cell arrest on the EC is modulated by shear rate, which is inversely- proportional to cell-cell contact time, rather than by the shear stress, which is proportional to the force exerted on formed bonds. β2 integrins/ICAM-1 adhesion mechanisms were examined and the results indicate LFA-1 and Mac-1 cooperate to mediate the PMN-EC-melanoma interactions under shear conditions. In addition, endogenously produced IL-8 contributes to PMN-facilitated melanoma arrest on the EC through the CXC chemokine receptors 1 and 2 (CXCR1 and CXCR2) on PMN. These results provide new evidence for the complex role of hemodynamic forces, secreted chemokines and PMN-melanoma adhesion in the recruitment of metastatic cancer cells to the EC.
AB - Previous studies have shown that neutrophils (PMNs) facilitate melanoma cell extravasation [M.J. Slattery, C. Dong, Neutrophils influence melanoma adhesion and migration under flow conditions, Intl. J. Cancer 106 (2003) 713-722] Little is known, however, about the specific interactions between PMNs, melanoma and the endothelium (EC) or the molecular mechanism involved under flow conditions. The aim of this study is to investigate a "two-step adhesion" hypothesis that involves initial PMN tethering on the EC and subsequent melanoma cells being captured by tethered PMNs. Different effects of hydrodynamic shear stress and shear rate were analyzed using a parallel-plate flow chamber. Results indicate a novel finding that PMN-facilitated melanoma cell arrest on the EC is modulated by shear rate, which is inversely- proportional to cell-cell contact time, rather than by the shear stress, which is proportional to the force exerted on formed bonds. β2 integrins/ICAM-1 adhesion mechanisms were examined and the results indicate LFA-1 and Mac-1 cooperate to mediate the PMN-EC-melanoma interactions under shear conditions. In addition, endogenously produced IL-8 contributes to PMN-facilitated melanoma arrest on the EC through the CXC chemokine receptors 1 and 2 (CXCR1 and CXCR2) on PMN. These results provide new evidence for the complex role of hemodynamic forces, secreted chemokines and PMN-melanoma adhesion in the recruitment of metastatic cancer cells to the EC.
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U2 - 10.1016/j.yexcr.2005.07.028
DO - 10.1016/j.yexcr.2005.07.028
M3 - Article
C2 - 16154563
AN - SCOPUS:26844469068
SN - 0014-4827
VL - 310
SP - 282
EP - 292
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 2
ER -
