Interaction between elastin and tumor cell lines with different metastatic potential; in vitro and in vivo studies |
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Authors: | J. Timar K. Lapis T. Fulop Z. S. Varga J. M. Tixier L. Robert W. Hornebeck |
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Affiliation: | (1) 1st Institute of Pathology and Experimental Cancer Research, The Semmelweis Medical University Budapest, ülli Út. 26, H-1085 Budapest, Hungary;(2) 1st Department of Medicine, Medical University, Debrecen, Hungary;(3) Laboratoire de Biologie de la Matrice Extracellulaire, UA CNRS 1174, Faculté Medicale, Université Paris-Val de Marne, 8 rue du Général Sarrail, F-94010 Créteil Cédex, France |
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Abstract: | Summary 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: -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 -elastin was used in order to study elastin-3LL-HM interaction. It was found to be saturable (2 ng3H-labelled -elastin/106 cells), with one class of high-affinity binding sites having Kd equal to 1.3 nM and 16000 sites/cell. The binding of -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 -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 -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 Mkelastin and the simultaneous i.v. injection into mice of 750 g -elastin together with the highly metastatic cells was able to reduce the number of lung colonies by more than 70% after 12 days.Abbreviations 3LL-HM, 3LL-LM highly metastatic and low-metastatic Lewis lung carcinoma cells |
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Keywords: | Elastin binding Elastin receptor Chemotaxis Ca2+ flux Lewis lung cell lines Cancer metastasis |
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