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HDGF: A Novel Factor in Multiple Myeloma Biology Identified

By: Sarah Campen, PharmD
Posted: Monday, August 29, 2022

Hepatoma-derived growth factor (HDGF), a protein present in extracellular vesicles released from human multiple myeloma cell lines, was recently identified as a novel factor with a biological role in multiple myeloma. A study published in Blood Advances revealed that HDGF may function to maintain multiple myeloma cell viability and to modify the tumor microenvironment. “HDGF is likely to play an important, albeit previously unrecognized, role in myeloma biology,” stated Dominique B. Hoelzinger, PhD, of the Mayo Clinic, Scottsdale, Arizona, and colleagues.

The researchers compared the extracellular vesicle protein cargo from human multiple myeloma cell lines with the protein cargo present in healthy plasma cells; the levels of HDGF were consistently higher in the multiple myeloma cell lines compared with plasma cells. Following HDGF knockdown, lower proliferation of human myeloma cell lines was observed. Conversely, AKT phosphorylation—a strong cell-survival signal—was activated when exogenous HDGF was added.

Metabolic analysis revealed that HDGF also seems to play a significant role in metabolism by enhancing the high glycolytic levels of human myeloma cell lines and significantly lowering mitochondrial respiration. These findings indicate that HDGF may play a role in myeloma cell survival and act in a paracrine manner on cells, such as macrophages and immature monocytes, in the bone marrow tumor microenvironment.

“Little is known about the function of HDGF in multiple myeloma,” noted the investigators. “The HDGF coding sequence is found on 1q21–23 and is part of the 1q amplification gene signature seen in some patients with multiple myeloma.”

Disclosure: The authors reported no conflicts of interests.

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