title: Interaction between elastin and tumor cell lines with different metastatic potential; in vitro and in vivo studies.
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: K-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 K-elastin was used in order to study elastin--3LL-HM interaction. It was found to be saturable (2 ng 3H-labelled K-elastin/10(6) cells), with one class of high-affinity binding sites having Kd equal to 1.3 nM and 16,000 sites/cell. The binding of K-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 K-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 K-elastin binding to 3LL-HM cells on their ability to form lung colonies in mice. It was shown that pretreatment of 10(4) 3LL-HM cells with 10 microM K-elastin and the simultaneous i.v. injection into mice of 750 micrograms K-elastin together with the highly metastatic cells was able to reduce the number of lung colonies by more than 70% after 12 days.
authors.affiliation: 1st Institute of Pathology and Experimental Cancer Research, Semmelweis Medical University Budapest, Hungary.
authors.forename: J
authors.initials: J
authors.lastname: Timar
authors.forename: K
authors.initials: K
authors.lastname: Lapis
authors.forename: T
authors.initials: T
authors.lastname: Fulop
authors.forename: Z S
authors.initials: ZS
authors.lastname: Varga
authors.forename: J M
authors.initials: JM
authors.lastname: Tixier
authors.forename: L
authors.initials: L
authors.lastname: Robert
authors.forename: W
authors.initials: W
authors.lastname: Hornebeck
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion; D002633:Chemotaxis; D004549:Elastin / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008175:Lung Neoplasms / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D010196:Pancreatic Elastase / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000201:enzymology / Q000378:metabolism*
chemical_list: D011956:Receptors, Cell Surface; C054901:elastin-binding proteins; D004549:Elastin; D010196:Pancreatic Elastase