inhibition of p-selectin and psgl-1 using humanized monoclonal antibodies increases the sensitivity of multiple myeloma cells to bortezomib

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2015
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Abstract
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.
Reference Key
muz2015biomedinhibition Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Barbara Muz;Feda Azab;Pilar de la Puente;Scott Rollins;Richard Alvarez;Ziad Kawar;Abdel Kareem Azab
Journal spectrochimica acta - part a: molecular and biomolecular spectroscopy
Year 2015
DOI
10.1155/2015/417586
URL
http://dx.doi.org/10.1155/2015/417586
Keywords
Medicine

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