Shear stress and shear rate differentially affect the multi-step process of leukocyte-facilitated melanoma adhesion.
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. Beta2 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.
Liang
Shile
S
The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16802-6804, USA.
Slattery
Margaret J
MJ
Dong
Cheng
C
D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D003470:Culture Media / Q000494:pharmacology; D003911:Dextrans / Q000494:pharmacology; D004727:Endothelium / Q000378:metabolism / Q000473:pathology; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D023062:Receptors, Interleukin-8A / Q000819:agonists; D023063:Receptors, Interleukin-8B / Q000819:agonists; D033081:Shear Strength; D013314:Stress, Mechanical; D014407:Tumor Cells, Cultured
D015815:Cell Adhesion Molecules; D003470:Culture Media; D003911:Dextrans; D016209:Interleukin-8; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B