Fibrin serves as a divalent ligand that regulates neutrophil-mediated melanoma cells adhesion to endothelium under shear conditions

Tugba Ozdemir, Pu Zhang, Changliang Fu, Cheng Dong

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Elevated soluble fibrin (sFn) levels are characteristic of melanoma hematogeneous dissemination, where tumor cells interact intimately with host cells. Melanoma adhesion to the blood vessel wall is promoted by immune cell arrests and tumor-derived thrombin, a serine protease that converts soluble fibrinogen (sFg) into sFn. However, the molecular requirement for sFn-mediated melanoma-polymorphonuclear neutrophils (PMNs) and melanoma-endothelial interactions under physiological flow conditions remain elusive. To understand this process, we studied the relative binding capacities of sFg and sFn receptors e.g., α v β 3 integrin and intercellular adhesion molecule-1 (ICAM-1) expressed on melanoma cells, ICAM-1 on endothelial cells (EC), and CD11b/ CD18 (Mac-1) on PMNs. Using a parallel-plate flow chamber, highly metastatic melanoma cells (1205Lu and A375M) and human PMNs were perfused over an EC monolayer expressing ICAM-1 in the presence of sFg or sFn. It was found that both the frequency and lifetime of direct melanoma adhesion or PMN-facilitated melanoma adhesion to the EC in a shear flow were increased by the presence of sFn in a concentration-dependent manner. In addition, sFn fragment D and plasmin-treated sFn failed to increase melanoma adhesion, implying that sFn-bridged cell adhesion requires dimer-mediated receptor- receptor cross-linking. Finally, analysis of the respective kinetics of sFn binding to Mac-1, ICAM-1, and α v β 3 by single bond cell tethering assays suggested that ICAM-1 and α v β 3 are responsible for initial capture and firm adhesion of melanoma cells. These results provide evidence that sFn enhances melanoma adhesion directly to ICAM-1 on the EC, while prolonged shear-resistant melanoma adhesion requires interactions with PMNs.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume302
Issue number8
DOIs
StatePublished - Apr 15 2012

Fingerprint

Fibrin
Cell Adhesion
Endothelium
Melanoma
Neutrophils
Ligands
Intercellular Adhesion Molecule-1
Endothelial Cells
Fibrinogen
CD146 Antigens
Fibrinolysin
Serine Proteases
Integrins
Thrombin
Blood Vessels
Neoplasms

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cell Biology

Cite this

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title = "Fibrin serves as a divalent ligand that regulates neutrophil-mediated melanoma cells adhesion to endothelium under shear conditions",
abstract = "Elevated soluble fibrin (sFn) levels are characteristic of melanoma hematogeneous dissemination, where tumor cells interact intimately with host cells. Melanoma adhesion to the blood vessel wall is promoted by immune cell arrests and tumor-derived thrombin, a serine protease that converts soluble fibrinogen (sFg) into sFn. However, the molecular requirement for sFn-mediated melanoma-polymorphonuclear neutrophils (PMNs) and melanoma-endothelial interactions under physiological flow conditions remain elusive. To understand this process, we studied the relative binding capacities of sFg and sFn receptors e.g., α v β 3 integrin and intercellular adhesion molecule-1 (ICAM-1) expressed on melanoma cells, ICAM-1 on endothelial cells (EC), and CD11b/ CD18 (Mac-1) on PMNs. Using a parallel-plate flow chamber, highly metastatic melanoma cells (1205Lu and A375M) and human PMNs were perfused over an EC monolayer expressing ICAM-1 in the presence of sFg or sFn. It was found that both the frequency and lifetime of direct melanoma adhesion or PMN-facilitated melanoma adhesion to the EC in a shear flow were increased by the presence of sFn in a concentration-dependent manner. In addition, sFn fragment D and plasmin-treated sFn failed to increase melanoma adhesion, implying that sFn-bridged cell adhesion requires dimer-mediated receptor- receptor cross-linking. Finally, analysis of the respective kinetics of sFn binding to Mac-1, ICAM-1, and α v β 3 by single bond cell tethering assays suggested that ICAM-1 and α v β 3 are responsible for initial capture and firm adhesion of melanoma cells. These results provide evidence that sFn enhances melanoma adhesion directly to ICAM-1 on the EC, while prolonged shear-resistant melanoma adhesion requires interactions with PMNs.",
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Fibrin serves as a divalent ligand that regulates neutrophil-mediated melanoma cells adhesion to endothelium under shear conditions. / Ozdemir, Tugba; Zhang, Pu; Fu, Changliang; Dong, Cheng.

In: American Journal of Physiology - Cell Physiology, Vol. 302, No. 8, 15.04.2012.

Research output: Contribution to journalArticle

TY - JOUR

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AU - Zhang, Pu

AU - Fu, Changliang

AU - Dong, Cheng

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AB - Elevated soluble fibrin (sFn) levels are characteristic of melanoma hematogeneous dissemination, where tumor cells interact intimately with host cells. Melanoma adhesion to the blood vessel wall is promoted by immune cell arrests and tumor-derived thrombin, a serine protease that converts soluble fibrinogen (sFg) into sFn. However, the molecular requirement for sFn-mediated melanoma-polymorphonuclear neutrophils (PMNs) and melanoma-endothelial interactions under physiological flow conditions remain elusive. To understand this process, we studied the relative binding capacities of sFg and sFn receptors e.g., α v β 3 integrin and intercellular adhesion molecule-1 (ICAM-1) expressed on melanoma cells, ICAM-1 on endothelial cells (EC), and CD11b/ CD18 (Mac-1) on PMNs. Using a parallel-plate flow chamber, highly metastatic melanoma cells (1205Lu and A375M) and human PMNs were perfused over an EC monolayer expressing ICAM-1 in the presence of sFg or sFn. It was found that both the frequency and lifetime of direct melanoma adhesion or PMN-facilitated melanoma adhesion to the EC in a shear flow were increased by the presence of sFn in a concentration-dependent manner. In addition, sFn fragment D and plasmin-treated sFn failed to increase melanoma adhesion, implying that sFn-bridged cell adhesion requires dimer-mediated receptor- receptor cross-linking. Finally, analysis of the respective kinetics of sFn binding to Mac-1, ICAM-1, and α v β 3 by single bond cell tethering assays suggested that ICAM-1 and α v β 3 are responsible for initial capture and firm adhesion of melanoma cells. These results provide evidence that sFn enhances melanoma adhesion directly to ICAM-1 on the EC, while prolonged shear-resistant melanoma adhesion requires interactions with PMNs.

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