Multiple myeloma cell lines and primary tumors proteome: protein biosynthesis and Immune system as potential therapeutic targets
Rodrigo Carlini Fernando1,*, Fabricio de Carvalho1,*, Diego Robles Mazzotti2, Adriane Feijó Evangelista3, Walter Moisés Tobias Braga1, Maria de Lourdes Chauffaille1, Adriana Franco Paes Leme4 and Gisele Wally Braga Colleoni1
1 Departamento de Oncologia Clínica e Experimental, Disciplina de Hematologia e Hemoterapia, Universidade Federal de São Paulo, UNIFESP, São Paulo, Brazil
2 Departamento de Psicobiologia, Universidade Federal de São Paulo, UNIFESP, São Paulo, Brazil
3 Fundação Pio XII - Hospital de Câncer de Barretos, Barretos, Brazil
4 Laboratório de Espectrometria de Massas, Laboratório Nacional de Biociências, LNBio, Conselho Nacional de Pesquisa em Energia e Materiais, CNPEM, Campinas, Brazil
* These authors have contributed equally to this manuscript
Correspondence:
Gisele Colleoni , email:
Keywords: multiple myeloma, proteomics, therapeutic targets
Received: June 30, 2015 Accepted: November 20, 2015 Published: November 24, 2015
Abstract
Despite great advance in multiple myeloma (MM) treatment since 2000s, it is still an incurable disease and novel therapies are welcome. Therefore, the purpose of this study was to explore MM plasma cells’ (MM-PC) proteome, in comparison with their normal counterparts (derived from palatine tonsils of normal donors, ND-PC), in order to find potential therapeutic targets expressed on the surface of these cells. We also aimed to evaluate the proteome of MM cell lines with different genetic alterations, to confirm findings obtained with primary tumor cells. Bone marrow (BM) samples from eight new cases of MM and palatine tonsils from seven unmatched controls were submitted to PC separation and, in addition to two MM cell lines (U266, RPMI-8226), were submitted to protein extraction for mass spectrometry analyses. A total of 81 proteins were differentially expressed between MM-PC and ND-PC - 72 upregulated and nine downregulated; U266 vs. RPMI 8226 cell lines presented 61 differentially expressed proteins - 51 upregulated and 10 downregulated. On primary tumors, bioinformatics analyses highlighted upregulation of protein biosynthesis machinery, as well as downregulation of immune response components, such as MHC class I and II, and complement receptors. We also provided comprehensive information about U266 and RPMI-8226 cell lines’ proteome and could confirm some patients’ findings.
