Dynamic CD138 surface expression regulates switch between myeloma growth and dissemination.

Area of Science:

• Oncology
• Cell Biology
• Immunology

Background:

• CD138 (syndecan-1) is a plasma cell marker with unclear in vivo function in myeloma.
• Myeloma cells exhibit heterogeneous CD138 expression, with distinct CD138-high and CD138-negative subsets.

Purpose of the Study:

• To investigate the functional role of CD138 expression in myeloma cell behavior in vivo.
• To explore the ontogeny and dynamic regulation of CD138 expression in myeloma.
• To assess the therapeutic potential of targeting CD138 in combination with chemotherapy.

Main Methods:

• Utilized a murine Vk*MYC myeloma model with heterogeneous CD138 expression.
• Compared proliferation, apoptosis, motility, and dissemination of CD138-high and CD138-negative myeloma cells.
• Investigated CD138 recycling via endocytic trafficking and its response to serum levels.
• Assessed the effect of CD138 neutralization and bortezomib combination therapy on myeloma progression.

Main Results:

• CD138-high myeloma cells showed increased proliferation, reduced apoptosis, enhanced IL-6R signaling, and better engraftment.
• CD138-negative myeloma cells exhibited higher motility, dissemination, and spread to other bones.
• CD138 neutralization induced myeloma cell migration, intravasation, and increased bone dissemination.
• Myeloma cells dynamically recycle CD138 surface expression in response to serum levels.
• Blocking CD138 enhanced bortezomib sensitivity and significantly reduced tumor size.

Conclusions:

• CD138 surface expression dynamically regulates a switch between myeloma cell growth and dissemination.
• Targeting CD138 offers a promising strategy to enhance chemotherapy efficacy and control myeloma progression.