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Alternatively spliced CD44 transcripts in diffuse large-cell lymphomas: characterization and comparison with normal
1Division of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115.
Blood
|December 15, 1993
Summary
CD44 variants, including exon 10, are differentially expressed in large-cell lymphomas (LCLs). Advanced LCLs show CD44 transcript patterns similar to activated B cells, suggesting roles in tumor cell trafficking.
Area of Science:
- Molecular biology
- Immunology
- Oncology
Background:
- CD44 is a cell surface glycoprotein with multiple alternatively spliced isoforms.
- The hematopoietic isoform (CD44H) is crucial for lymphocyte homing.
- Aberrant CD44 variant expression is implicated in epithelial carcinoma metastasis.
Purpose of the Study:
- To investigate CD44 transcript variants in large-cell lymphomas (LCLs) compared to normal B cells and epithelial cells.
- To determine if specific CD44 isoforms correlate with lymphoma stage or location.
- To understand the role of CD44 variant expression in lymphoid and epithelial malignancy trafficking.
Main Methods:
- Semiquantitative RNA-based polymerase chain reaction (PCR) was used to analyze CD44 mRNA.
- Specific CD44 variants were identified by size, exon-specific probes, and sequence analysis.
- Samples included primary nodal, extranodal, and disseminated LCLs, normal Ig-activated splenic B cells, and epithelial cells.
Main Results:
- Extranodal and disseminated LCLs exhibited increased CD44H and novel exon 10-containing isoforms compared to nodal LCLs.
- CD44 transcripts in advanced LCLs resembled those in normal activated B cells.
- Epithelial malignancies showed reduced CD44H and increased larger CD44 variants.
Conclusions:
- Specific CD44 splicing variants are differentially expressed in LCLs, correlating with disease dissemination.
- The CD44 expression profile in advanced LCLs mirrors that of activated B cells, suggesting a role in immune cell-like trafficking.
- Regulated CD44 variant expression likely influences the migration and spread of both lymphoid and epithelial malignancies.