The communication between multiple myeloma cells and healthy bone marrow cells is an important step in disease progression, researchers have found, showing that multiple myeloma cells can cause changes in the nonmalignant bone marrow constituents that support the growth of malignant cells.
The study, “Multiple myeloma cells promote migration of bone marrow mesenchymal stem cells by altering their translation initiation,” published in the Journal of Leukocyte Biology, shows that multiple myeloma takes over the bone marrow healthy cells by affecting the initiation of the protein translation process (creating a protein from a messenger RNA molecule), and suggests that this process may be targeted to halt the development of the disease.
“Our research should help identify therapeutic targets that may be used to minimize the collateral damage,” Mahmoud Dabbah, the study’s first author, said in a press release. “The identification of the translation initiation phase as a dialogue platform affords a potential new therapeutic target to be explored,” he said.
Mesenchymal stem cells (MSCs), the cells that give rise to bone cells, fat cells, muscle cells and cartilage cells, are important constituents of the bone marrow niche. Studies have reported that bone marrow MSCs are aberrant in multiple myeloma, that they cross-talk with the malignant cells and participate in disease processes. One of the pathologic aspects of MSC transformation in multiple myeloma is the osteolytic lesions, or bone lesions, that cause patients severe bone pain.
To understand how multiple myeloma cells induce such transformation in bone marrow MSCs, the researchers cultured multiple myeloma cells with mesenchymal stem cells isolated from healthy donors. They found that multiple myeloma cells can profoundly affect their adjacent MSCs, causing a twofold increase in their transcriptional activity (protein synthesis), and enhancing the expression of particular factors that stimulate the growth of malignant cells.
In addition, results also revealed that multiple myeloma cells induced a fourfold increase in the migration of MSCs, which was supported by an increase in the expression of two microRNAs: miR-119b and miR-125a.
But the effects were reversible, as removing multiple myeloma cells from the MSC culture allowed the MSCs to acquire a normal transcription and migration pattern. The researchers now warrant further studies to identify clinical relevant targets that can block this crosstalk and improve multiple myeloma therapies.
“These studies delve into the crosstalk between tumors and the surrounding microenvironment for multiple myeloma and reveal a new type of influence by tumors on normal cells,” said E. John Wherry, PhD, deputy editor of the Journal of Leukocyte Biology. “The finding that protein translation in normal cells in subverted by tumor cells to create a better growth environment for cancer cells should reveal new opportunities for therapeutics aimed at stopping this process,” Wherry wrote.