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
- M. V. Lomonosov Moscow State University
Leninskie Gory, 1/12, Moscow, Russian Federation, 119991 - LIA LFR20 French-Russian Joint Cancer Research Laboratory
Villejuif, France–Moscow, Russian Federation - 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
Full text: (PDF, in English)
References
[1]
van Zijl F, Krupitza G, Mikulits W. Initial steps of metastasis: cell invasion and endothelial transmigration. Mutat Res. 2011; 728(1-2):23-34.
[2]
Liotta LA. Adhere, Degrade, and Move: The three-step model of invasion. Cancer Res. 2016; 76(11):3115-7.
[3]
Tremblay P-L, Huot J, Auger F A. Mechanisms by which E-selectin regulates diapedesis of colon cancer cells under flow conditions. Cancer Res. 2008; 68(13):5167-76.
[4]
St Hill C. Interactions between endothelial selectins and cancer cells regulate metastasis. Front Biosci. 2011; 16:3233-51.
[5]
Wirtz D, Konstantopoulos K, Searson PC. The physics of cancer: the role of physical interactions and mechanical forces in metastasis. Nat Rev Cancer. 2011; 11(7):512-22.
[6]
Borsig L, Wong R, Hynes RO, Varki NM, Varki A. Synergistic effects of L- and P-selectin in facilitating tumor metastasis can involve non-mucin ligands and implicate leukocytes as enhancers of metastasis. Proc Natl Acad Sci U S A. 2002; 99(4):2193-8.
[7]
Varki NM, Varki A. Diversity in cell surface sialic acid presentations: implications for biology and disease. Lab Invest. 2007; 87(9):851-7.
[8]
Gehlsen KR1, Davis GE, Sriramarao P. Integrin expression in human melanoma cells with differing invasive and metastatic properties. Clin Exp Metastasis. 1992; 10(2):111-20.
[9]
Hynes RO. Integrins: bidirectional, allosteric signaling machines. Cell. 2002; 110(6):673-87.
[10]
McAuley JL, Linden SK, Png CW, King RM, Pennington HL, Gendler SJ, Florin TH, Hill JR, Korolik V, McGuckin MA. MUC1 cell surface mucin is a critical element of the mucosal barrier to infection. J Clin Invest. 2007; 117(8):2313-24.
[11]
Ligtenberg MJ, Buijs F, Vos HL, Hilkens J. Suppression of cellular aggregation by high levels of episialin. Cancer Res. 1992; 52(8):2318-24
[12]
Wesseling J, van der Valk SW, Hilkens J. A mechanism for inhibition of E-cadherin-mediated cell-cell adhesion by the membrane-associated mucin episialin/MUC1. Mol Biol Cell. 1996; 7(4):565-77.
[13]
Feng H, Ghazizadeh M, Konishi H, Araki T. Expression of MUC1 and MUC2 mucin gene products in human ovarian carcinomas. Jpn J Clin Oncol. 2002; 32(12):525-9.
[14]
Wesseling J, van der Valk SW, Vos HL, Sonnenberg A, Hilkens J. Episialin (MUC1) overexpression inhibits integrin-mediated cell adhesion to extracellular matrix components. J Cell Biol. 1995; 129(1):255-65.
[15]
Zhao Q, Barclay M, Hilkens J, Guo X, Barrow H, Rhodes JM, Yu LG. Interaction between circulating galectin-3 and cancer-associated MUC1 enhances tumour cell homotypic aggregation and prevents anoikis. Mol Cancer. 2010; 9:154.
[16]
Rahn JJ1, Shen Q, Mah BK, Hugh JC. MUC1 initiates a calcium signal after ligation by intercellular adhesion molecule-1. J Biol Chem. 2004; 279(28):29386-90.
[17]
Mori Y, Akita K, Yashiro M, Sawada T, Hirakawa K, Murata T, Nakada H. Binding of galectin-3, a β-galactoside-binding lectin, to MUC1 protein enhances phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt, promoting tumor cell malignancy. J Biol Chem. 2015; 290(43):26125-40.
[18]
Geng Y, Yeh K, Takatani T, King MR. Three to tango: MUC1 as a ligand for both E-selectin and ICAM-1 in the breast cancer metastatic cascade. Front Oncol. 2012; 2:76
[19]
Rahn JJ, Chow JW, Horne GJ, Mah BK, Emerman JT, Hoffman P, Hugh JC. MUC1 mediates transendothelial migration in vitro by ligating endothelial cell ICAM-1. Clin Exp Metastasis. 2005; 22(6):475483.
[20]
Paszek MJ, DuFort CC, Rossier O, Bainer R, Mouw JK, Godula K, Hudak JE, Lakins JN, Wijekoon AC, Cassereau L, Rubashkin MG, Magbanua MJ, Thorn KS, Davidson MW, Rugo HS, Park JW, Hammer DA, Giannone G, Bertozzi CR, Weaver VM. The cancer glycocalyx mechanically primes integrin-mediated growth and survival. Nature. 2014; 511(7509):319-25.
[21]
Syrkina M, Viushkov V, Potashnikova D, Veiko V, Vassetzky Y, Rubtsov M. From an increase in the number of tandem repeats through the decrease of sialylation to the downregulation of MUC1 expression level. J Cell Biochem. 2019; 120(3):4472-84.
[22]
Syrkina MS, Maslakova AA, Potashnikova DM, Veiko VP, Vassetzky YS, Rubtsov MA. Dual Role of the extracellular domain of human mucin MUC1 in metastasis. J Cell Biochem. 2017; 118(11):4002-11.