Deregulation such as overexpression of adhesion molecules influences cancer progression and survival. Metastasis of malignant cells from their primary tumor site to distant organs is the most common reason for cancer-related deaths. Junctional adhesion molecule (JAM)-C, a member of the Ig-like JAM family, can homodimerize and aid cancer cell migration and metastasis. Here we show that this molecule is dynamically expressed on multiple myeloma (MM) cells in the marrow and co-localizes with blood vessels within the bone marrow of mice and humans. Additionally, JAM-C upregulation inversely correlates with the downregulation of the canonical plasma cell marker CD138 (syndecan-1), whose surface expression has recently been found to dynamically regulate a switch between MM growth in situ and MM dissemination. Moreover, targeting JAM-C in a syngeneic in vivo MM model ameliorates MM progression and improves outcome. Overall, our data demonstrate that JAM-C might serve not only as an additional novel diagnostic biomarker but also as a therapeutic target in MM disease.

Junctional adhesion molecule-C expression specifies a CD138low/neg multiple myeloma cell population in mice and humans / A. Brandl, A. Solimando, Z. Mokhtari, P. Tabares, J. Medler, H. Manz, M.C. DA VIA', G.A. Croci, M. Kurzwart, S. Thusek, T. Schneider, R. Ebert, F. Jakob, H. Einsele, A. Beilhack. - In: BLOOD ADVANCES. - ISSN 2473-9529. - (2021 Dec 03). [Epub ahead of print] [10.1182/bloodadvances.2021004354]

Junctional adhesion molecule-C expression specifies a CD138low/neg multiple myeloma cell population in mice and humans

M.C. DA VIA'
Investigation
;
G.A. Croci;
2022

Abstract

Deregulation such as overexpression of adhesion molecules influences cancer progression and survival. Metastasis of malignant cells from their primary tumor site to distant organs is the most common reason for cancer-related deaths. Junctional adhesion molecule (JAM)-C, a member of the Ig-like JAM family, can homodimerize and aid cancer cell migration and metastasis. Here we show that this molecule is dynamically expressed on multiple myeloma (MM) cells in the marrow and co-localizes with blood vessels within the bone marrow of mice and humans. Additionally, JAM-C upregulation inversely correlates with the downregulation of the canonical plasma cell marker CD138 (syndecan-1), whose surface expression has recently been found to dynamically regulate a switch between MM growth in situ and MM dissemination. Moreover, targeting JAM-C in a syngeneic in vivo MM model ameliorates MM progression and improves outcome. Overall, our data demonstrate that JAM-C might serve not only as an additional novel diagnostic biomarker but also as a therapeutic target in MM disease.
multiple myeloma; junctional adhesion molecule; CD138; mouse model; metastasis
Settore MED/15 - Malattie del Sangue
3-dic-2021
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/892428
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