Inhibition of platelets and tumor cell adhesion by the disintegrin domain of human ADAM9 to collagen I under dynamic flow conditions.
This work aimed to investigate the role of the disintegrin domain of the human ADAM9 (ADAM9D) on the adhesion of breast tumor cells and platelets to collagen I, in a dynamic flow assay to simulate in vivo shear conditions. Recombinant ADAM9D was able to support tumor cell adhesion through binding to the beta1 integrin subunit and also to inhibit the invasion through matrigel in vitro. In a dynamic flow assay ADAM9D inhibited about 75% and 65% of MDA-MB-231 tumor cells and platelet adhesion to collagen I, respectively. In addition, it was demonstrated that alphaVbeta3 integrin is new interacting partner for ADAM9D. In conclusion, these results suggest a role for the disintegrin domain of ADAM9 in the metastatic process. Also, ADAM9D may be a tool for investigating the role of ADAMs in metastasis and cancer progression and for the design of selective inhibitors against the adhesion and extravasation of cancer cells.
Cominetti
Marcia R
MR
Departamento de Ciências Fisiológicas, Universidade Federal de São Carlos, SP, Brazil. mcominetti@ufscar.br
Martin
Ana Carolina B M
AC
Ribeiro
Juliana U
JU
Djaafri
Ibtissem
I
Fauvel-Lafève
Françoise
F
Crépin
Michel
M
Selistre-de-Araujo
Heloisa S
HS
D051722:ADAM Proteins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D003094:Collagen / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism*; D019483:Disintegrins / Q000378:metabolism*; D004338:Drug Combinations; D004727:Endothelium / Q000378:metabolism; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D011509:Proteoglycans / Q000378:metabolism; D051381:Rats
D024042:Collagen Type I; D019483:Disintegrins; D004338:Drug Combinations; D039302:Integrin alphaVbeta3; D007797:Laminin; D008565:Membrane Proteins; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D051722:ADAM Proteins; C098339:ADAM9 protein, human