title: Comparable roles of CD44v8-10 and CD44s in the development of bone metastases in a mouse model.
abstract: Cluster of differentiation (CD)44 has been implicated in cancer metastasis to bone. Clinical and experimental studies have suggested that the standard isoform of CD44 (CD44s) and the variant isoform of CD44 (CD44v) enhance metastasis. The present study examined the differential roles of CD44s and CD44v, particularly CD44v8-10, in the development of bone metastases. For this purpose, MDA-MB-231 human breast cancer cells and A549 human lung cancer cells were stably transduced with epithelial splicing regulatory protein 1 (ESRP1), which regulates the alternative splicing of several genes, including CD44. The introduction of ESRP1 induced a splicing switch from CD44s to CD44v, particularly to CD44v8-10, while the total amount of CD44 was rarely affected. However, ESRP1 did not significantly affect cell proliferation, migration, invasion or tumor sphere formationin vitro. Furthermore, ESRP1 did not cause significant differences in the development of bone metastases in a mouse model. As an alternative approach, cancer cells transduced with the CD44v8-10 gene were also established. The overexpression of CD44v8-10 in MCF-7 human breast cancer cells, which rarely express any isoform of CD44, promoted cell migration and sphere formation, whereas the overexpression of CD44v8-10 in MDA-MB-231 cells, which endogenously express high levels of CD44s, did not exert these effects. The results of the present study collectively suggest that the ability of CD44v8-10 to promote tumor aggressiveness and bone metastases is similar to that of CD44s. CD44v8-10 and CD44s may represent potential therapeutic targets for the treatment of bone metastases.
authors.affiliation: Department of Histology and Cell Biology, Matsumoto Dental University, Nagano 399-0781, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Hiraga
authors.affiliation: Department of Histology and Cell Biology, Matsumoto Dental University, Nagano 399-0781, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nakamura
keywords: CD44s; CD44v8-10; ESRP1; bone metastases; cancer stem cells