Newly Uncovered Role for Protein in Multiple Myeloma
Hyaluronan and proteoglycan link protein 1 (HAPLN1) may activate a bortezomib-resistant nuclear factor–kappa B (NF-κB) signaling pathway and induce resistance to bortezomib in patients with multiple myeloma, according to a study published by Shigeki Miyamoto, PhD, of the McArdle Laboratory of Cancer Research, University of Wisconsin-Madison, and colleagues in the Journal of Biological Chemistry. The researchers also found that increased levels of HAPLN1 may be detected in the bone marrow plasma and bone marrow stromal cells in patients with multiple myeloma.
NF-κB is a family of transcription factors that play a key role in cell survival and proliferation in multiple myeloma. Bortezomib suppresses this pathway by stabilizing its inhibitor. HAPLN1, an extracellular matrix protein, was found to have strong proteasome inhibitor–resistant NF-κB–inducing activities.
Full-length HAPLN1 lacked signaling activity but contained biologically active signaling fragments, called ‘matrikines,’ which may be released when the protein was processed. Thus, “the development of methodologies to accurately quantify HAPLN1-matrikine levels in individual multiple myeloma patients could serve as a new biomarker for multiple myeloma therapy and drug resistance,” proposed Dr. Miyamoto and colleagues.
HAPLN1 is also expressed in other tissues, including the brain, heart, and digestive tract, and its overexpression has been linked to colorectal, breast, and hepatocellular cancers. Therefore, the investigators suggest further study to uncover how HAPLN1 may be involved in the NF-κB pathways in people with such types of cancer.