A Directly Spliced Exon 10-Containing CD44 Variant Promotes the
Metastasis and Homotypic Aggregation of Aggressive Non-Hodgkin's
Lymphoma
Yoshihiro Yakushijin,
Joshua Steckel,
Samir Kharbanda,
Robert Hasserjian,
Donna Neuberg,
Wei-meng Jiang,
Ian Anderson, and
Margaret A. Shipp
From the Divisions of Hematologic Malignancies and Biostatistics,
Dana-Farber Cancer Institute; and the Departments of Medicine and
Pathology, Harvard Medical School, Boston, MA.
Variants of the CD44 cell-surface adhesion molecule include
additional sequences encoded by combinations of exons from the membrane
proximal domain (exons 6-14). Preliminary studies suggest that these
additional variable membrane proximal sequences may alter the ligand
specificity, glycosylation, and biologic function of CD44. In earlier
studies, we found that primary extranodal and widely disseminated
aggressive non-Hodgkin's lymphomas (NHLs) and normal activated B cells
expressed a directly spliced exon 10-containing variant (CD44ex10),
whereas normal resting B cells expressed larger exon 10-containing
variants (CD44ex10-14 and CD44ex7-14). To obtain additional information
regarding the function of exon 10-containing CD44 variants in
aggressive NHL, we generated aggressive NHL transfectants that
expressed CD44ex10, CD44ex10-14, CD44ex7-14, the standard CD44 isoform
(CD44H), or vector alone, and evaluated the local tumorogenicity,
aggregation, and metastatic potential of these transfectants. CD44ex10
aggressive NHL transfectants were more likely to cause local tumor
formation in nude mice than transfectants expressing the larger exon
10-containing variants, CD44H, or vector alone. In addition, cell
suspensions derived from CD44ex10 local tumors exhibited far greater
homotypic aggregation than those obtained from other CD44 or
vector-only local tumors. In nude mice that received CD44ex10
transfectants, distant metastases were also significantly more likely
to develop than in animals that were given either the CD44ex10-14,
CD44ex7-14, CD44H, or vector-only transfectants. These data provide the
first evidence that the directly spliced exon 10-containing CD44
variant (CD44ex10) has a unique biologic function in aggressive NHL.
Blood, Vol. 91 No. 11 (June 1), 1998:
pp. 4282-4291
© 1998 by The American Society of Hematology.
