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Enforced CD19 expression leads to growth inhibition and reduced tumorigenicity
M S Mahmoud1, R Fujii, H Ishikawa
1Department of Immunohematology, Yamaguchi University School of Medicine, Ube, Japan.
Abstract:
In multiple myeloma (MM), the cell surface protein, CD19, is specifically lost while it continues to be expressed on normal plasma cells. To examine the biological significance of loss of CD19 in human myeloma, we have generated CD19 transfectants of a tumorigenic human myeloma cell line (KMS-5). The CD19 transfectants showed slower growth rate in vitro than that of control transfectants. They also showed a lower capability for colony formation as evaluated by anchorage-independent growth in soft agar assay. The CD19 transfectants also had reduced tumorigenicity in vivo when subcutaneously implanted into severe combined immunodeficiency (SCID)-human interleukin-6 (hIL-6) transgenic mice. The growth-inhibitory effect was CD19-specific and probably due to CD19 signaling because this effect was not observed in cells transfected with a truncated form of CD19 that lacks the cytoplasmic signaling domain. The in vitro growth-inhibitory effect was confirmed in a nontumorigenic human myeloma cell line (U-266). However, introduction of the CD19 gene into a human erythroleukemia cell line (K-562) also induced growth inhibition, suggesting that this effect is CD19-specific, but not restricted to myeloma cells. These data suggest that the specific and generalized loss of CD19 in human myeloma cells could be an important factor contributing to the proliferation of the malignant plasma cell clones in this disease.
Insights
The loss of CD19, a cell surface protein, in multiple myeloma (MM) may contribute to cancer cell proliferation. Restoring CD19 expression inhibits myeloma cell growth and tumorigenicity.
Area of Science:
- Immunology
- Molecular Biology
- Cancer Research
Background:
- Multiple myeloma (MM) is characterized by the specific loss of CD19 on malignant plasma cells, while normal plasma cells retain CD19 expression.
- The biological significance of CD19 loss in MM pathogenesis remains unclear.
Purpose of the Study:
- To investigate the functional role of CD19 in human myeloma cells.
- To determine if CD19 expression influences myeloma cell growth, proliferation, and tumorigenicity.
Main Methods:
- Generation of CD19-transfected human myeloma cell lines (KMS-5 and U-266).
- Assessment of in vitro growth rates and anchorage-independent growth (soft agar assay).
- Evaluation of in vivo tumorigenicity in SCID-hIL-6 transgenic mice.
Main Results:
- CD19 transfectants exhibited slower in vitro growth and reduced colony formation compared to controls.
- CD19-expressing cells demonstrated decreased tumorigenicity in vivo.
- The growth-inhibitory effect was CD19-specific and dependent on its cytoplasmic signaling domain.
- Similar growth inhibition was observed in a non-myeloma cell line (K-562), indicating a broader CD19-mediated effect.
Conclusions:
- The specific loss of CD19 in multiple myeloma may promote the proliferation of malignant plasma cells.
- CD19 signaling exerts a general growth-inhibitory effect on hematopoietic cells, including myeloma cells.