Investigating the Role of Bone Marrow Adipocyte-Secreted Proteins in Multiple Myeloma Cell Metabolism and Signaling
Document Type
Event
Faculty Mentor
Allyson Schimelman
Abstract
Multiple myeloma (MM) is a plasma cell malignancy characterized by low remission rates and strong interactions with the bone marrow microenvironment. Obesity is a major risk factor for MM and is associated with increased abundance and size of bone marrow adipocytes (BMAds). Previous studies have demonstrated that BMAds support MM cell growth and proliferation; however, the mechanisms underlying this support remain poorly understood. Preliminary data from our laboratory suggest that conditioned media (CM) derived from human patient-derived BMAds induces a metabolic shift in MM cells compared to standard culture media. We hypothesized that BMAd-secreted proteins contribute to these phenotypic changes. To investigate this, a mass spectrometry–based proteomics screen was performed to identify proteins differentially expressed in MM cells following treatment with BMAd-CM and mesenchymal stem cell (MSC)-CM. Preliminary results indicate enrichment of proteins associated with inflammatory signaling pathways, cytoskeletal organization, and osteoclastic activity. To validate these findings, MM cells were treated with conditioned media from multiple BMAd donors for up to 96 hours. Cells were then harvested for RNA extraction and protein purification for downstream analysis using qRT-PCR, with additional analyses including ELISA, and flow cytometry as needed. The goal of this work is to clarify the molecular processes by which BMAds affect the signaling and phenotype of MM cells. Understanding these interactions may reveal novel therapeutic targets for disrupting tumor-supportive processes within the bone marrow microenvironment.
Investigating the Role of Bone Marrow Adipocyte-Secreted Proteins in Multiple Myeloma Cell Metabolism and Signaling
Multiple myeloma (MM) is a plasma cell malignancy characterized by low remission rates and strong interactions with the bone marrow microenvironment. Obesity is a major risk factor for MM and is associated with increased abundance and size of bone marrow adipocytes (BMAds). Previous studies have demonstrated that BMAds support MM cell growth and proliferation; however, the mechanisms underlying this support remain poorly understood. Preliminary data from our laboratory suggest that conditioned media (CM) derived from human patient-derived BMAds induces a metabolic shift in MM cells compared to standard culture media. We hypothesized that BMAd-secreted proteins contribute to these phenotypic changes. To investigate this, a mass spectrometry–based proteomics screen was performed to identify proteins differentially expressed in MM cells following treatment with BMAd-CM and mesenchymal stem cell (MSC)-CM. Preliminary results indicate enrichment of proteins associated with inflammatory signaling pathways, cytoskeletal organization, and osteoclastic activity. To validate these findings, MM cells were treated with conditioned media from multiple BMAd donors for up to 96 hours. Cells were then harvested for RNA extraction and protein purification for downstream analysis using qRT-PCR, with additional analyses including ELISA, and flow cytometry as needed. The goal of this work is to clarify the molecular processes by which BMAds affect the signaling and phenotype of MM cells. Understanding these interactions may reveal novel therapeutic targets for disrupting tumor-supportive processes within the bone marrow microenvironment.
