JAM-C as a switch for multiple myeloma dissemination
A new study, published by Andreas Brandl and our team in Blood Advances today, reveals that Junctional Adhesion Molecule C (JAM-C) plays a critical role in the progression and dissemination of multiple myeloma (MM), marking a significant advancement in our understanding of this aggressive blood cancer.
Reciprocal regulation of JAM-C and CD138 switches programs in multiple myeloma cells. Brandl A. et al. Blood Advances 2022
In an interdisciplinary approach, senior scientist Andreas Brandl, PhD, and colleagues have discovered that JAM-C specifically marks a subset of MM cells with low or absent CD138 expression (CD138low/neg), distinguishing them within the bone marrow of both human patients and in MM mouse models. Targeting JAM-C in preclinical models showed a promising reduction in MM progression and dissemination, indicating that JAM-C inhibitors could complement existing treatments and offer new therapeutic avenues.
The study uncovered that JAM-C expression on MM cells correlates inversely with CD138, a canonical cell surface receptor associated with plasma cells. This inverse relationship pinpoints a potential mechanism through which MM cells transition between localized growth and widespread dissemination. Upregulation of JAM-C was observed to facilitate the migration and metastasis of MM cells, a crucial step in cancer spread. Blocking JAM-C in a murine model of MM led to a significant reduction in disease severity, MM dissemination and cancer burden.
Lead Researcher Dr. Andreas Brandl states, “Our research shows that targeting JAM-C could be a pivotal strategy in controlling multiple myeloma progression. This could lead to more personalized and effective treatments for patients suffering from this challenging disease.” The scientist proposes that JAM-C could serve as both, a novel diagnostic biomarker and therapeutic target in MM. He envisions the development of treatments that specifically inhibit JAM-C, potentially enhancing patient outcomes when used alongside conventional therapies such as proteasome inhibitors and monoclonal antibodies.
The new findings result from a collaborative effort by scientists within the SPP consortium µbone of the German Research Council (DFG), the FORTITHER research network of the Bayerische Forschungsstiftung, the Interdisciplinary Center for Clinical Research Würzburg, and international research partners.
Reference:
Brandl A, Solimando AG, Mokhtari Z, Tabares P, Medler P, Manz H, Da Via M, Croci GA, Kurzwart M, Thusek S, Schneider T, Ebert R, Jakob F, Einsele H, Beilhack A. (2022). Junctional Adhesion Molecule-C expression specifies a CD138low/neg multiple myeloma cell population in mice and men. Blood Advances 6(7):2195-2206.