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CXCR3-binding chemokines in multiple myeloma
Antonio Pellegrino1, Francesco Antonaci, Francesca Russo
1Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari, Policlinico, Piazza Giulio Cesare 11, Bari I-70124, Italy.
Cancer Letters
|April 10, 2004
Summary
Multiple myeloma (MM) cells express the CXCR3 receptor, which binds chemokines I-TAC, Mig, and IP10. This interaction promotes MM cell invasion and metastasis by increasing tyrosine-kinase phosphorylation and matrix metalloproteinase secretion.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- CXC chemokines (I-TAC, Mig, IP10) and their receptor CXCR3 are implicated in advanced tumor progression, invasion, and metastasis.
- Understanding the role of the CXCR3/chemokine axis in multiple myeloma (MM) is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the expression of CXCR3 on multiple myeloma cell lines and patient samples.
- To determine the functional consequences of CXCR3/chemokine interaction on MM cell progression, including tyrosine-kinase phosphorylation, proliferation, chemotaxis, and matrix metalloproteinase (MMP) secretion.
Main Methods:
- Fluorescence-activated cell sorting (FACS) was used to analyze CXCR3 expression on four MM cell lines and bone marrow plasma cells from 20 MM patients.
- Functional assays were performed to assess tyrosine-kinase phosphorylation, proliferation, chemotaxis, and MMP-2/MMP-9 secretion following stimulation with I-TAC, Mig, and IP10.
Main Results:
- CXCR3 expression was detected on 75% of MM cell lines and 90% of patient samples.
- I-TAC, Mig, and IP10 induced tyrosine-kinase phosphorylation and chemotaxis in MM cells.
- The CXCR3/chemokine interaction increased MMP-2 and MMP-9 secretion, but did not affect proliferation.
Conclusions:
- The CXCR3/chemokine axis is expressed in multiple myeloma and plays a significant role in promoting tumor progression.
- Targeting the CXCR3/chemokine pathway may represent a viable strategy to inhibit MM dissemination and metastasis.