Cooperative disengagement of fas and intercellular adhesion molecule-1 function in neoplastic cells confers enhanced colonization efficiency

Kebin Liu, Sheila A. Caldwell, Scott I. Abrams

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Understanding the mechanisms of tumor progression is crucial toward the development of therapeutic interventions. Although the loss of sensitivity to cell death is a hallmark of neoplastic progression, it is likely one of several essential features that underlie a malignantly proficient or aggressive tamorigenic phenotype. Here, we identified intercellular adhesion molecule-1 (ICAM-1) as a molecule with expression coordinately regulated with Fas and inversely correlated with malignant phenotype between matched pairs of differentially aggressive malignant subpopulations in three mouse models. To determine whether coordinate expression of Fas and ICAM-1 regulated malignant behavior, tumor sublines were produced that expressed either lower levels of both Fas and ICAM-1, lower levels of Fas, or lower levels of ICAM-1 and then assessed for metastatic lung tumor growth. Tumor sublines rendered both Fas incompetent and ICAM-1 incompetent displayed significantly higher numbers of tumor nodules compared with tumor sublines separately expressing low levels of Fas or ICAM-1. However, all tumor sublines regardless of their Fas and ICAM-1 levels comparably infiltrated the lung, suggesting that Fas- and ICAM-1-based interactions ultimately influenced lung colonization efficiency. Overall, these data suggested that both Fas and ICAM-1 pathways cooperated to regulate tumor progression and that the coordinate down-regulation of Fas and ICAM-1 intensified malignant progression at the level of colonization. Thus, a FaS loICAM-1lo phenotype may be characteristic of at least certain advancing, immune-resistant neoplastic subpopulations.

Original languageEnglish (US)
Pages (from-to)1045-1054
Number of pages10
JournalCancer Research
Volume65
Issue number3
StatePublished - Feb 1 2005
Externally publishedYes

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Intercellular Adhesion Molecule-1
Neoplasms
Phenotype
Lung
Cell Death
Down-Regulation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Cooperative disengagement of fas and intercellular adhesion molecule-1 function in neoplastic cells confers enhanced colonization efficiency. / Liu, Kebin; Caldwell, Sheila A.; Abrams, Scott I.

In: Cancer Research, Vol. 65, No. 3, 01.02.2005, p. 1045-1054.

Research output: Contribution to journalArticle

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