Low expression of neural cell adhesion molecule, CD56, is associated with low efficacy of bortezomib plus dexamethasone therapy in multiple myeloma

• Published in: PloS one Vol. 13; no. 5; p. e0196780
• Main Authors: Yoshida, Takashi, Ri, Masaki, Kinoshita, Shiori, Narita, Tomoko, Totani, Haruhito, Ashour, Reham, Ito, Asahi, Kusumoto, Shigeru, Ishida, Takashi, Komatsu, Hirokazu, Iida, Shinsuke
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 08.05.2018; Public Library of Science (PLoS)
• Subjects: Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Apoptosis; Apoptosis - drug effects; Biology and Life Sciences; Biomarkers; Bone marrow; Bortezomib; Bortezomib - administration & dosage; Bortezomib - pharmacology; CD56 Antigen - biosynthesis; CD56 Antigen - genetics; Cell adhesion; Cell adhesion & migration; Cell Line, Tumor; Chemotherapy; Cytotoxicity; Dexamethasone; Dexamethasone - administration & dosage; Dosage and administration; Drug dosages; Drug Resistance, Neoplasm; Drug therapy; Endoplasmic Reticulum Stress - drug effects; Gene expression; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Genetic aspects; Growth factors; Hematology; Humans; Inhibitor drugs; Leukemia; Lymphoma; Medical prognosis; Medicine and Health Sciences; Multiple myeloma; Multiple Myeloma - drug therapy; Multiple Myeloma - metabolism; Neoplasm Proteins - biosynthesis; Neoplasm Proteins - genetics; Oncology; Patient outcomes; Plasma; Proteasome Inhibitors - administration & dosage; Proteasome Inhibitors - pharmacology; Research and Analysis Methods; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; RNA, Neoplasm - biosynthesis; RNA, Neoplasm - genetics; Steroids; Studies; Targeted cancer therapy; Transfection; Transplants & implants; Treatment Outcome; Ubiquitinated Proteins - metabolism; University graduates; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0196780

Bortezomib (Btz) is an active agent used to treat multiple myeloma (MM). Not all patients who receive Btz-containing therapy show a favorable response. Interaction of cellular adhesion molecules with MM and bone marrow stromal cells is crucial for the survival of MM cells. However, little is known about the role of these molecules in the sensitivity of MM to Btz-containing therapy. Thus, we evaluated the correlation between the level of cellular adhesion molecules in MM cells and the efficacy of Btz plus dexamethasone (Bd) therapy. The expression of the neural cell adhesion molecule gene (NCAM, also known as CD56), ITGA4, CXCR4, and other genes were analyzed in 74 samples of primary MM cells collected from patients before they received Bd therapy. Of the eight genes tested, expression of NCAM was lower among patients who responded poorly to Bd therapy. In vitro expression of NCAM induced by transfection of MM cells enhanced their sensitivity to Btz treatment by causing accumulation of polyubiquitinated proteins. Our results indicate that expression of NCAM is associated with better response to Btz treatment and is a promising candidate biomarker for predicting response to therapies involving Btz.