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Antitumor potential of fibulin-5 in breast cancer cells depends on its RGD cell adhesion motif

dc.contributor.authorMohamedi Y.
dc.contributor.authorFontanil T.
dc.contributor.authorCobo T.
dc.contributor.authorVega J.A.
dc.contributor.authorCobo J.L.
dc.contributor.authorPérez-Basterrechea M.
dc.contributor.authorCobo J.
dc.contributor.authorObaya Á.J.
dc.contributor.authorCal S.
dc.date.accessioned2020-09-02T22:23:04Z
dc.date.available2020-09-02T22:23:04Z
dc.date.issued2019
dc.identifier10.33594/000000123
dc.identifier.citation53, 1, 87-100
dc.identifier.issn10158987
dc.identifier.urihttps://hdl.handle.net/20.500.12728/5355
dc.descriptionBackground/Aims: Different components of the tumor microenvironment can be either tumor-promoting or tumor-suppressive agents depending on factors which are not fully understood. Fibulins are components of the extracellular matrix from different tissues and constitute a clear example of this dual function. In fact, fibulins may either support tumor growth or abolish progression of malignant cells depending on the crosstalk between tumor cells and their surrounding stroma through mechanisms that remain to be elucidated. Among all fibulins, fibulin-5 contains a particular structural hallmark which consists in the presence of a RGD motif within its architecture. Previous reports have highlighted the importance of the interaction of this motif with integrins, and not only in normal functions but also in a tumor context. Methods: Site-Directed Mutagenesis technique was employed to introduce the change RGD to RGE (RGD-to-RGE) within Fbln5 cDNA sequence. Cell proliferation was measured using the MTT assay or by counting Ki-67 positive cell nuclei. Cell adhesion was analysed using culture plates coated with different extracellular matrix components. Cell invasion was evaluated using 24-well Matrigel-coated invasion chambers, and mammosphere formation was monitored using ultralow attachment culture plates. BALB/c mice were employed to induce subcutaneous tumors. Results: The RGD-to-RGE change alters the capacity of breast cancer cells to adhere to different extracellular matrix proteins as well as to αvβ3 and α5β1 integrins, and promotes protumor effects using different cell-based assays. Moreover, 4T1 cells, a mouse breast cancer cell line model, shows an increased capacity to generate tumors when exogenously expresses fibulin-5 with a RGD-to-RGE change, and such capacity is similar to that shown for 4T1 cells with an interfered Fbln5 gene. Conclusion: These data highlight the importance of the RGD motif of fibulin-5 to induce antitumor effects and provide new insights into the involvement of fibulins in tumor processes. © 2019 The Author(s).
dc.language.isoen
dc.publisherCell Physiol Biochem Press GmbH & Co KG
dc.subjectBreast cancer
dc.subjectFibulin
dc.subjectRGD motif
dc.subjectTumor microenvironment
dc.subjectarginylglycylaspartic acid
dc.subjectarginylglycylglutamine
dc.subjectcomplementary DNA
dc.subjectfibulin 5
dc.subjectscleroprotein
dc.subjecttripeptide
dc.subjectunclassified drug
dc.subjectvery late activation antigen 5
dc.subjectvitronectin receptor
dc.subjectarginyl-glycyl-aspartic acid
dc.subjectcadherin
dc.subjectFBLN5 protein, human
dc.subjectoligopeptide
dc.subjectrecombinant protein
dc.subjectscleroprotein
dc.subjectvimentin
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectantineoplastic activity
dc.subjectArticle
dc.subjectbreast cancer
dc.subjectbreast cancer cell line
dc.subjectcarcinogenesis
dc.subjectcell adhesion
dc.subjectcell culture
dc.subjectcell proliferation
dc.subjectcell viability assay
dc.subjectcontrolled study
dc.subjectDNA sequence
dc.subjectextracellular matrix
dc.subjectFbln5 gene
dc.subjectgene
dc.subjecthuman
dc.subjecthuman cell
dc.subjectmale
dc.subjectmouse
dc.subjectMTT assay
dc.subjectnonhuman
dc.subjectpriority journal
dc.subjectprotein expression
dc.subjectprotein function
dc.subjectprotein motif
dc.subjectprotein protein interaction
dc.subjectsite directed mutagenesis
dc.subjectallotransplantation
dc.subjectanimal
dc.subjectBagg albino mouse
dc.subjectbiosynthesis
dc.subjectbreast tumor
dc.subjectcell motion
dc.subjectdrug effect
dc.subjectfemale
dc.subjectgenetics
dc.subjectmetabolism
dc.subjectneoplasm
dc.subjectpathology
dc.subjecttumor cell line
dc.subjectAnimals
dc.subjectBreast Neoplasms
dc.subjectCadherins
dc.subjectCell Adhesion
dc.subjectCell Line, Tumor
dc.subjectCell Movement
dc.subjectCell Proliferation
dc.subjectExtracellular Matrix Proteins
dc.subjectFemale
dc.subjectHumans
dc.subjectMale
dc.subjectMice
dc.subjectMice, Inbred BALB C
dc.subjectMutagenesis, Site-Directed
dc.subjectNeoplasms
dc.subjectOligopeptides
dc.subjectRecombinant Proteins
dc.subjectTransplantation, Homologous
dc.subjectVimentin
dc.titleAntitumor potential of fibulin-5 in breast cancer cells depends on its RGD cell adhesion motif
dc.typeArticle


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