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Alternatively spliced CD44 transcripts in diffuse large-cell lymphomas:
characterization and comparison with normal activated B cells and
epithelial malignancies
G Salles, M Zain, WM Jiang, VA Boussiotis and MA Shipp
Division of Medical Oncology, Dana Farber Cancer Institute, Boston, MA
02115.
CD44 exists in a variety of alternatively spliced isoforms that include
variable numbers of additional exons from the membrane proximal domain
(exons 6-14). Lymphocytes express high levels of a "hematopoietic" isoform
(CD44H) with no additional variable exons. CD44H binds lymphocytes to
postcapillary venules and promotes lymphocyte extravasation into nodal
areas. Epithelial carcinomas also express CD44 variants, including exon
10-containing isoforms associated with metastasis in a rat model. An exon
10-containing CD44 isoform is also transiently expressed by normal
activated lymphocytes, suggesting that the protein may function in the
trafficking of both normal lymphocytes and metastatic tumors. To identify
the specific CD44 transcripts in tumors from patients with primary nodal,
extranodal, and disseminated large-cell lymphomas (LCLs) and compare them
with CD44 mRNAs in normal Ig-activated splenic B cells and epithelial
cells, we used a semiquantitative RNA-based polymerase chain reaction.
Specific CD44 variants were identified by size, hybridization with
exon-specific probes, and sequence analysis. In comparison to primary nodal
LCLs, extranodal and disseminated LCLs had increased levels of CD44H and
additional isoforms, including a directly spliced (exon 5-->exon 10--
>exon 15) exon 10-containing CD44 variant. The CD44 transcripts in
extranodal and advanced-stage LCLs were similar to those in normal Ig-
activated splenic B cells, whereas epithelial malignancies contained
decreased CD44H and increased amounts of larger CD44 variants with
additional exons from the membrane proximal domain. The regulated
expression of specific CD44 variants is likely to influence the trafficking
of lymphoid and epithelial malignancies.
Volume 82,
Issue 12,
pp. 3539-3547,
12/15/1993
Copyright © 1993 by The American Society of Hematology
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