Hydrodynamic shear rate regulates melanoma-leukocyte aggregation, melanoma adhesion to the endothelium, and subsequent extravasation

Shile Liang, Margaret J. Slattery, Desiree Wagner, Scott I. Simon, Cheng Dong

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Adhesion to and subsequent extravasation through the endothelial lining of blood vessels is critical for tumor cells to establish metastases. Recent studies have indicated that polymorphonuclear neutrophils (PMNs) may enhance melanoma adhesion to the endothelium (EC) and subsequent extravasation under dynamic flow conditions. However, little is known about hydrodynamics involved in the tumor microenvironment within the microcirculation. In this study, effects of hydrodynamic flow on regulating melanoma cell adhesion to the EC have been investigated. Results indicate that under flow conditions, interactions between melanoma cells and the EC are distinctly different from PMN-EC interactions. Without expressions of surface integrins or sialylated molecules, most melanoma cells that express a high-level of intercellular adhesion molecule (ICAM-1) are not able to effectively adhere to the inflamed EC by themselves. Binding of melanoma cells and PMNs through ICAM-1 on melanoma cells and β2 integrins on PMNs has been shown to enhance melanoma cell arrest on the EC. Although PMN tethering on the EC is regulated by both the shear rate and shear stress, melanoma cell adhesion to the EC and subsequent extravasation via tethering PMN on the EC is predominantly regulated by shear rate, which partly is due to the shear-rate-dependent PMN-melanoma aggregation in shear flow. These findings provide a rationale and mechanistic basis for understanding of leukocyte-tumor cell interactions under flow conditions during tumor cell extravasation and metastasis.

Original languageEnglish (US)
Pages (from-to)661-671
Number of pages11
JournalAnnals of Biomedical Engineering
Volume36
Issue number4
DOIs
StatePublished - Apr 2008

Fingerprint

Shear deformation
Tumors
Adhesion
Agglomeration
Hydrodynamics
Cell adhesion
Cells
Microcirculation
Molecules
Blood vessels
Shear flow
Linings
Shear stress

Keywords

  • β integrins
  • ICAM-1
  • Melanoma metastasis
  • Neutrophil
  • Shear flow

ASJC Scopus subject areas

  • Biomedical Engineering

Cite this

Hydrodynamic shear rate regulates melanoma-leukocyte aggregation, melanoma adhesion to the endothelium, and subsequent extravasation. / Liang, Shile; Slattery, Margaret J.; Wagner, Desiree; Simon, Scott I.; Dong, Cheng.

In: Annals of Biomedical Engineering, Vol. 36, No. 4, 04.2008, p. 661-671.

Research output: Contribution to journalArticle

Liang, Shile ; Slattery, Margaret J. ; Wagner, Desiree ; Simon, Scott I. ; Dong, Cheng. / Hydrodynamic shear rate regulates melanoma-leukocyte aggregation, melanoma adhesion to the endothelium, and subsequent extravasation. In: Annals of Biomedical Engineering. 2008 ; Vol. 36, No. 4. pp. 661-671.
@article{47e63e0cd4f54c8daf40f8781945c6df,
title = "Hydrodynamic shear rate regulates melanoma-leukocyte aggregation, melanoma adhesion to the endothelium, and subsequent extravasation",
abstract = "Adhesion to and subsequent extravasation through the endothelial lining of blood vessels is critical for tumor cells to establish metastases. Recent studies have indicated that polymorphonuclear neutrophils (PMNs) may enhance melanoma adhesion to the endothelium (EC) and subsequent extravasation under dynamic flow conditions. However, little is known about hydrodynamics involved in the tumor microenvironment within the microcirculation. In this study, effects of hydrodynamic flow on regulating melanoma cell adhesion to the EC have been investigated. Results indicate that under flow conditions, interactions between melanoma cells and the EC are distinctly different from PMN-EC interactions. Without expressions of surface integrins or sialylated molecules, most melanoma cells that express a high-level of intercellular adhesion molecule (ICAM-1) are not able to effectively adhere to the inflamed EC by themselves. Binding of melanoma cells and PMNs through ICAM-1 on melanoma cells and β2 integrins on PMNs has been shown to enhance melanoma cell arrest on the EC. Although PMN tethering on the EC is regulated by both the shear rate and shear stress, melanoma cell adhesion to the EC and subsequent extravasation via tethering PMN on the EC is predominantly regulated by shear rate, which partly is due to the shear-rate-dependent PMN-melanoma aggregation in shear flow. These findings provide a rationale and mechanistic basis for understanding of leukocyte-tumor cell interactions under flow conditions during tumor cell extravasation and metastasis.",
keywords = "β integrins, ICAM-1, Melanoma metastasis, Neutrophil, Shear flow",
author = "Shile Liang and Slattery, {Margaret J.} and Desiree Wagner and Simon, {Scott I.} and Cheng Dong",
year = "2008",
month = "4",
doi = "10.1007/s10439-008-9445-8",
language = "English (US)",
volume = "36",
pages = "661--671",
journal = "Annals of Biomedical Engineering",
issn = "0090-6964",
publisher = "Springer Netherlands",
number = "4",

}

TY - JOUR

T1 - Hydrodynamic shear rate regulates melanoma-leukocyte aggregation, melanoma adhesion to the endothelium, and subsequent extravasation

AU - Liang, Shile

AU - Slattery, Margaret J.

AU - Wagner, Desiree

AU - Simon, Scott I.

AU - Dong, Cheng

PY - 2008/4

Y1 - 2008/4

N2 - Adhesion to and subsequent extravasation through the endothelial lining of blood vessels is critical for tumor cells to establish metastases. Recent studies have indicated that polymorphonuclear neutrophils (PMNs) may enhance melanoma adhesion to the endothelium (EC) and subsequent extravasation under dynamic flow conditions. However, little is known about hydrodynamics involved in the tumor microenvironment within the microcirculation. In this study, effects of hydrodynamic flow on regulating melanoma cell adhesion to the EC have been investigated. Results indicate that under flow conditions, interactions between melanoma cells and the EC are distinctly different from PMN-EC interactions. Without expressions of surface integrins or sialylated molecules, most melanoma cells that express a high-level of intercellular adhesion molecule (ICAM-1) are not able to effectively adhere to the inflamed EC by themselves. Binding of melanoma cells and PMNs through ICAM-1 on melanoma cells and β2 integrins on PMNs has been shown to enhance melanoma cell arrest on the EC. Although PMN tethering on the EC is regulated by both the shear rate and shear stress, melanoma cell adhesion to the EC and subsequent extravasation via tethering PMN on the EC is predominantly regulated by shear rate, which partly is due to the shear-rate-dependent PMN-melanoma aggregation in shear flow. These findings provide a rationale and mechanistic basis for understanding of leukocyte-tumor cell interactions under flow conditions during tumor cell extravasation and metastasis.

AB - Adhesion to and subsequent extravasation through the endothelial lining of blood vessels is critical for tumor cells to establish metastases. Recent studies have indicated that polymorphonuclear neutrophils (PMNs) may enhance melanoma adhesion to the endothelium (EC) and subsequent extravasation under dynamic flow conditions. However, little is known about hydrodynamics involved in the tumor microenvironment within the microcirculation. In this study, effects of hydrodynamic flow on regulating melanoma cell adhesion to the EC have been investigated. Results indicate that under flow conditions, interactions between melanoma cells and the EC are distinctly different from PMN-EC interactions. Without expressions of surface integrins or sialylated molecules, most melanoma cells that express a high-level of intercellular adhesion molecule (ICAM-1) are not able to effectively adhere to the inflamed EC by themselves. Binding of melanoma cells and PMNs through ICAM-1 on melanoma cells and β2 integrins on PMNs has been shown to enhance melanoma cell arrest on the EC. Although PMN tethering on the EC is regulated by both the shear rate and shear stress, melanoma cell adhesion to the EC and subsequent extravasation via tethering PMN on the EC is predominantly regulated by shear rate, which partly is due to the shear-rate-dependent PMN-melanoma aggregation in shear flow. These findings provide a rationale and mechanistic basis for understanding of leukocyte-tumor cell interactions under flow conditions during tumor cell extravasation and metastasis.

KW - β integrins

KW - ICAM-1

KW - Melanoma metastasis

KW - Neutrophil

KW - Shear flow

UR - http://www.scopus.com/inward/record.url?scp=40949101283&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=40949101283&partnerID=8YFLogxK

U2 - 10.1007/s10439-008-9445-8

DO - 10.1007/s10439-008-9445-8

M3 - Article

VL - 36

SP - 661

EP - 671

JO - Annals of Biomedical Engineering

JF - Annals of Biomedical Engineering

SN - 0090-6964

IS - 4

ER -