Biopolym. Cell. 2019; 35(4):288-302.
Structure and Function of Biopolymers
The length of mucin MUC1 extracellular domain affects integrin-mediated cell adhesion to fibronectin and vitronectin
1, 2Syrkina M. S., 1Potashnikova D. M., 1, 2, 3Rubtsov M. A.
  1. M. V. Lomonosov Moscow State University
    Leninskie Gory, 1/12, Moscow, Russian Federation, 119991
  2. LIA LFR20 French-Russian Joint Cancer Research Laboratory
    Villejuif, France–Moscow, Russian Federation
  3. I. M. Sechenov First Moscow State Medical University,
    8, Trubetskaya Str. Moscow, Russian Federation, 119991

Abstract

Aim. To determine whether the adhesion capacity of extracellular matrix proteins differs in cells stably expressing a recombinant fusion proteins containing different number of tandem repeats from the extracellular region of the human mucin MUC1. Methods. Cell adhesion assay, FACS analysis, confocal fluorescence microscopy. Results. With an increase in the number of tandem repeats in the extracellular region of MUC1, the uniform distribution of the protein in the region of contact with glass first changes to discrete, and then compact clusters are formed. Cell adhesion to vitronectin and fibronectin does not depend on the presence of integrin receptors on the cell surface and decreases in the following order: HT-29_TR4 → HT-29_TR12. For HT-29_TR20 cells, an increase in adhesion to these extracellular matrix proteins is observed. Integrins avb3 (vitronectin receptors) form clusters in all the cell lines analyzed, but integrins a5b1 (fibronectin receptors) form compact clusters only on the surface of HT-29_TR20 cells. Both integrins appear in the areas devoid of recombinant MUC1 molecules on the surface of HT-29_TR4, HT-29_TR12 and HT-29_TR20 cells and their distribution on the surface of HT-29_TR- cells does not depend on the recombinant protein localization. Conclusions. An increase in the number of repeats in the extracellular region of MUC1 from 12 to 20 leads to a noticeable decrease in the antagonism of mucin MUC1 with the integrin avb3 in the cell adhesion to vitronectin and an appearance a synergism with the integrin a5b1 in the cell adhesion to fibronectin
Keywords: MUC1, integrin, avb3, a5b1, adhesion, clustering

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