Adhesion and Signaling of Tumor Cells to Leukocytes and Endothelium in Cancer Metastasis

Research output: Chapter in Book/Report/Conference proceedingChapter

4 Scopus citations

Abstract

Heterotypic cell–cell adhesion in the near wall region under dynamic shear forces has been studied. In particular, we focus on neutrophil (PMN)–melanoma cell emboli formation in a non-linear shear flow and subsequent tethering to the vascular endothelium (EC) as a result of cell–cell aggregation. The extent of tumor cell adhesion to a vessel wall is governed by the kinetic formation/disruption of receptor–ligand bonds, soluble signaling proteins within the tumor microenvironment, and the hydrodynamic shear within the circulation. Upon tumor cell arrest on the endothelium, retraction of EC during tumor cell extravasation occurs due to the disruption of intercellular channels or disassembly of the vascular endothelial (VE)-cadherin homodimers that allow the passage of soluble proteins and cells. Preliminary studies have found tumor-elicited PMNs increase melanoma cell extravasation, which involves PMNs tethering on the EC and subsequently capturing/maintaining melanoma cells in close proximity to the EC. Results have indicated a novel finding that PMN-facilitated melanoma cell arrest on the EC is mediated by binding between the intercellular adhesion molecule (ICAM)-1 (expressing on both melanoma cells and ECs) and β2 integrins on PMNs, influenced by tumor-induced inflammatory cytokines, e.g., interleukin (IL)-8, and hydrodynamic shear rates. Furthermore, the adherens junctions in terms of VE-cadherin are regulated by endothelial mitogen activated protein kinases (MAPK) in response to tumor cell adhesion to the EC, as well as to IL-8 and several other soluble signaling proteins within the tumor microenvironment. These studies will yield new evidence for the complex role of hemodynamics, protein signaling, and heterotypic cell adhesion in the recruitment of metastatic cancer cells to the EC in the microcirculation during metastasis, which will be significant in fostering new cross-disciplinary approaches to cancer treatment.

Original languageEnglish (US)
Title of host publicationStudies in Mechanobiology, Tissue Engineering and Biomaterials
PublisherSpringer
Pages477-521
Number of pages45
DOIs
StatePublished - Jan 1 2011

Publication series

NameStudies in Mechanobiology, Tissue Engineering and Biomaterials
Volume4
ISSN (Print)1868-2006
ISSN (Electronic)1868-2014

All Science Journal Classification (ASJC) codes

  • Biomedical Engineering
  • Mechanics of Materials
  • Biomaterials
  • Biotechnology
  • Biophysics
  • Medicine (miscellaneous)

Fingerprint Dive into the research topics of 'Adhesion and Signaling of Tumor Cells to Leukocytes and Endothelium in Cancer Metastasis'. Together they form a unique fingerprint.

  • Cite this

    Dong, C. (2011). Adhesion and Signaling of Tumor Cells to Leukocytes and Endothelium in Cancer Metastasis. In Studies in Mechanobiology, Tissue Engineering and Biomaterials (pp. 477-521). (Studies in Mechanobiology, Tissue Engineering and Biomaterials; Vol. 4). Springer. https://doi.org/10.1007/8415_2010_21