Tumor Microenvironment Proteomics: Lessons From Multiple Myeloma

Abstract

Although the “seed and soil” hypothesis was proposed by Stephen Paget at the end of the 19th century, where he postulated that tumor cells (seeds) need a propitious medium (soil) to be able to establish metastases, only recently the tumor microenvironment started to be more studied in the field of Oncology. Multiple myeloma (MM), a malignancy of plasma cells, can be considered one of the types of cancers where there is more evidence in the literature of the central role that the bone marrow (BM) microenvironment plays, contributing to proliferation, survival, migration, and drug resistance of tumor cells. Despite all advances in the therapeutic arsenal for MM treatment in the last years, the disease remains incurable. Thus, studies aiming a better understanding of the pathophysiology of the disease, as well as searching for new therapeutic targets are necessary and welcome. Therefore, the present study aimed to evaluate the protein expression profiling of mononuclear cells derived from BM of MM patients in comparison with these same cell types derived from healthy individuals, in order to fill this gap in MM treatment. Proteomic analysis was performed using the mass spectrometry technique and further analyses were done using bioinformatics tools, to identify dysregulated biological pathways and/or processes in the BM microenvironment of patients with MM as a result of the disease. Among the pathways identified in this study, we can highlight an upregulation of proteins related to protein biosynthesis, especially chaperone proteins, in patients with MM. Additionally, we also found an upregulation of several proteins involved in energy metabolism, which is one of the cancer hallmarks. Finally, with regard to the downregulated proteins, we can highlight mainly those involved in different pathways of the immune response, corroborating the data that has demonstrated that the immune system of MM is impaired and, therefore, the immunotherapies that have been studied recently for the treatment of the disease are extremely necessary in the search for a control and a cure for these patients who live with the disease.