RUX also downregulates the expression of CXCL12, CXCR4, MUC1, and CD44 in MM cells and monocytes co-cultured with MM tumour cells; overexpression of these genes is associated with resistance of MM cells to the immunomodulatory agent lenalidomide.
CD44-specific A6 short peptide (KPSSPPEE) functionalized polymersomal epirubicin (A6-PS-EPI), which boosts targetability and anticancer efficacy toward human multiple myeloma (MM) in vivo, is described.
Our results showed that BP-loaded HA-CCMs exhibit markedly enhanced toleration, broadened therapeutic window, and significantly more effective growth suppression of CD44-overexpressed multiple myeloma in nude mice than free bortezomib.
Here, we show that a novel pan-HDACi AR-42 downregulates CD44, a glycoprotein that has been associated with lenalidomide and dexamethasone resistance in myeloma both in vitro and in vivo.
Taken together, our findings support the hypotheses that CD44 and CAM-DR contribute to lenalidomide resistance in multiple myeloma, that CD44 should be evaluated as a putative biomarker of sensitivity to lenalidomide, and that ATRA or other approaches that target CD44 may overcome clinical lenalidomide resistance.
Furthermore, we found defective actin assembly and down-regulation of the adhesion receptor CD44 in MM HSPCs functionally reflected by impaired migration and adhesion.
CD138 (Syndecan 1) is a heparan sulfate proteoglycan that concentrates heparan sulfate-binding growth factors on the surface of normal and malignant plasma cells (multiple myeloma, MMC).
Using four bona fide myeloma cell lines (KHM-1B, KMS12-BM, RPMI8226 and U266) and primary myeloma cells, we identified CD29 (beta1-integrin), CD44, CD49d (alpha4-integrin, a subunit of VLA-4), CD54 (intercellular adhesion molecule-1 (ICAM-1)), CD138 (syndecan-1) and CD184 (CXC chemokine receptor-4 (CXCR4)) as major adhesion molecules expressed on MM. shRNA-mediated knockdown of CD49d but not CD44, CD54, CD138 and CD184 significantly reversed CAM-DR of myeloma cells to bortezomib, vincristine, doxorubicin and dexamethasone.
Myeloma tumors are characterized by high expression of syndecan-1 (CD138), a heparan sulfate proteoglycan present on the myeloma cell surface and shed into the tumor microenvironment.
In addition, when myeloma cells were coincubated with 50 microM etodolac on bone marrow stromal cells (BMSCs), myeloma cell adhesion to BMSCs was significantly inhibited compared with thalidomide or meloxicam coincubation, and the adhesion molecules VLA-4, LFA-1 (CD11a), CXCX4, and CD44 were suppressed on myeloma cells treated with etodolac.
Expression of CD44v9-containing isoforms (CD44v9) on myeloma plasma cells correlates with unfavorable prognosis, suggesting that CD44 variant molecules are involved in the disease process.
We report on the different expression of CD56 and CD44 in plasma cells (PCs) simultaneously collected from bone marrow, extramedullary locations and peripheral blood in seven patients with multiple myeloma.
Expression of CD44v9-containing isoforms (CD44v9) on myeloma plasma cells correlates with unfavorable prognosis, suggesting that CD44 variant molecules are involved in the disease process.
We have shown that MM cells express the cell surface adhesion molecules CD29/CDw49d(VLA-4), CD18/CD11a(LFA-1) and CD44, and may localize to marrow via specific adherence to both extracellular matrix proteins and to bone marrow stromal cells (BMSCs).