Inhibition of P-Selectin and PSGL-1 Using Humanized Monoclonal Antibodies Increases the Sensitivity of Multiple Myeloma Cells to Bortezomib
Joint Authors
Muz, Barbara
Azab, Feda
de la Puente, Pilar
Rollins, Scott
Alvarez, Richard
Kawar, Ziad
Azab, Abdel Kareem
Source
Issue
Vol. 2015, Issue 2015 (31 Dec. 2015), pp.1-8, 8 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-10-11
Country of Publication
Egypt
No. of Pages
8
Main Subjects
Abstract EN
Multiple myeloma (MM) is a plasma cell malignancy localized in the bone marrow.
Despite the introduction of novel therapies majority of MM patients relapse.
We have previously shown that inhibition of P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1) play a key role in proliferation of MM and using small-molecule inhibitors of P-selectin/PSGL-1 sensitized MM cells to therapy.
However, these small-molecule inhibitors had low specificity to P-selectin and showed poor pharmacokinetics.
Therefore, we tested blocking of P-selectin and PSGL-1 using functional monoclonal antibodies in order to sensitize MM cells to therapy.
We have demonstrated that inhibiting the interaction between MM cells and endothelial and stromal cells decreased proliferation in MM cells and in parallel induced loose-adhesion to the primary tumor site to facilitate egress.
At the same time, blocking this interaction in vivo led to MM cells retention in the circulation and delayed homing to the bone marrow, thus exposing MM cells to bortezomib which contributed to reduced tumor growth and better mice survival.
This study provides a better understanding of the biology of P-selectin and PSGL-1 and their roles in dissemination and resensitization of MM to treatment.
American Psychological Association (APA)
Muz, Barbara& Azab, Feda& de la Puente, Pilar& Rollins, Scott& Alvarez, Richard& Kawar, Ziad…[et al.]. 2015. Inhibition of P-Selectin and PSGL-1 Using Humanized Monoclonal Antibodies Increases the Sensitivity of Multiple Myeloma Cells to Bortezomib. BioMed Research International،Vol. 2015, no. 2015, pp.1-8.
https://search.emarefa.net/detail/BIM-1055409
Modern Language Association (MLA)
Muz, Barbara…[et al.]. Inhibition of P-Selectin and PSGL-1 Using Humanized Monoclonal Antibodies Increases the Sensitivity of Multiple Myeloma Cells to Bortezomib. BioMed Research International No. 2015 (2015), pp.1-8.
https://search.emarefa.net/detail/BIM-1055409
American Medical Association (AMA)
Muz, Barbara& Azab, Feda& de la Puente, Pilar& Rollins, Scott& Alvarez, Richard& Kawar, Ziad…[et al.]. Inhibition of P-Selectin and PSGL-1 Using Humanized Monoclonal Antibodies Increases the Sensitivity of Multiple Myeloma Cells to Bortezomib. BioMed Research International. 2015. Vol. 2015, no. 2015, pp.1-8.
https://search.emarefa.net/detail/BIM-1055409
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1055409