Shear stress and shear rate differentially affect the multi-step process of leukocyte-facilitated melanoma adhesion

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)282-292
Number of pages11
JournalExperimental Cell Research
Volume310
Issue number2
DOIs
StatePublished - Nov 1 2005

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this