Interaction between elastin and tumor cell lines with different metastatic potential; in vitro and in vivo studies

J. Timar, K. Lapis, T. Fulop, Z. S. Varga, J. M. Tixier, L. Robert, W. Hornebeck

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Interactions between the extracellular matrix macromolecules and tumor cells are critical in the process of metastasis formation. We show here that elastins (both mature insoluble elastin and a 75-kDa soluble peptide: κ-elastin) adhere rapidly to two cell lines with high metastatic capacities: a metastatic lung carcinoma cell line (3LL-HM) and a human amelanotic melanoma cell line (A-2058); by contrast the low-metastatic Lewis lung carcinoma cell line variant as well as a rhabdomyosarcoma cell line with a low metastatic potential bind to elastins to a much lower extent.3H-labelled κ-elastin was used in order to study elastin-3LL-HM interaction. It was found to be saturable (2 ng3H-labelled κ-elastin/106 cells), with one class of high-affinity binding sites having Kd equal to 1.3 n M and 16000 sites/cell. The binding of κ-elastin to 3LL-HM cells at its receptor triggered several cell responses; (a) increase of intracellular Ca2+ concentration; (b) induction of 3LL-HM chemotaxis toward the κ-elastin gradient; (c) stimulation of the adherence of mature insoluble elastin. In contrast to non-transformed cells such as fibroblasts and smooth muscle cells, the adhesion kinetics of insoluble elastin to 3LL-HM did not exhibit a lag period; the rapid binding of insoluble elastin to the tumor cells was followed by its slow detachment from the cells, which lasted for 6 h. 3LL-HM cells but not human skin fibroblasts were shown to secrete elastinolytic activity inhibitable by metal-chelating agents. In vivo studies were performed in order to evaluate the influence of κ-elastin binding to 3LL-HM cells on their ability to form lung colonies in mice. It was shown that pretreatment of 104 3LL-HM cells with 10 ΜMkelastin and the simultaneous i.v. injection into mice of 750 Μg κ-elastin together with the highly metastatic cells was able to reduce the number of lung colonies by more than 70% after 12 days.

Original languageEnglish
Pages (from-to)232-238
Number of pages7
JournalJournal of cancer research and clinical oncology
Volume117
Issue number3
DOIs
Publication statusPublished - May 1 1991

Keywords

  • Ca flux
  • Cancer metastasis
  • Chemotaxis
  • Elastin binding
  • Elastin receptor
  • Lewis lung cell lines

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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