Functional role of CD44v-xCT system in the development of spasmolytic polypeptide-expressing metaplasia

Takeyuki Wada, Takatsugu Ishimoto, Ryo Seishima, Kenji Tsuchihashi, Momoko Yoshikawa, Hiroko Oshima, Masanobu Oshima, Takashi Masuko, Nicholas A. Wright, Satoshi Furuhashi, Kotaro Hirashima, Hideo Baba, Yuko Kitagawa, Hideyuki Saya, Osamu Nagano

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Cancer development is often preceded by the appearance of preneoplastic lesions. In gastric carcinogenesis, chronic inflammation and histopathologic progression of the stomach epithelium lead to the development of metaplasia and eventually adenocarcinoma. The cell surface protein CD44, especially its variant isoforms (CD44v), has been implicated in metaplasia-carcinoma sequence progression in the stomach. We recently found that CD44v interacts with and stabilizes xCT, a subunit of the cystine transporter system xc(-), in cancer cells and thereby increases cystine uptake and confers resistance to various types of cellular stress in vivo. The functional relevance of CD44v and xCT in the development of preneoplastic lesions, however, has remained unknown. We have now examined the role of the CD44v-xCT system in the development of spasmolytic polypeptide-expressing metaplasia (SPEM) in mouse models of gastric carcinogenesis. CD44v was found to be expressed de novo in SPEM, and CD44v+ metaplastic cells manifested upregulation of xCT expression compared with CD44v- cells. Genetic ablation of CD44 or treatment with sulfasalazine, an inhibitor of xCT-dependent cystine transport, suppressed the development of SPEM and subsequent gastric tumor growth. Therapy targeted to CD44v-xCT could thus prove effective for prevention or attenuation of the CD44v-dependent development of preneoplastic lesions and cancer.

Original languageEnglish
Pages (from-to)1323-1329
Number of pages7
JournalCancer Science
Volume104
Issue number10
DOIs
Publication statusPublished - Oct 1 2013
Externally publishedYes

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Metaplasia
Stomach
Cystine
Neoplasms
Carcinogenesis
Sulfasalazine
Protein Isoforms
Membrane Proteins
Adenocarcinoma
Up-Regulation
Epithelium
spasmolytic polypeptide
Inflammation
Carcinoma
Growth

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

Cite this

Wada, T., Ishimoto, T., Seishima, R., Tsuchihashi, K., Yoshikawa, M., Oshima, H., ... Nagano, O. (2013). Functional role of CD44v-xCT system in the development of spasmolytic polypeptide-expressing metaplasia. Cancer Science, 104(10), 1323-1329. https://doi.org/10.1111/cas.12236

Functional role of CD44v-xCT system in the development of spasmolytic polypeptide-expressing metaplasia. / Wada, Takeyuki; Ishimoto, Takatsugu; Seishima, Ryo; Tsuchihashi, Kenji; Yoshikawa, Momoko; Oshima, Hiroko; Oshima, Masanobu; Masuko, Takashi; Wright, Nicholas A.; Furuhashi, Satoshi; Hirashima, Kotaro; Baba, Hideo; Kitagawa, Yuko; Saya, Hideyuki; Nagano, Osamu.

In: Cancer Science, Vol. 104, No. 10, 01.10.2013, p. 1323-1329.

Research output: Contribution to journalArticle

Wada, T, Ishimoto, T, Seishima, R, Tsuchihashi, K, Yoshikawa, M, Oshima, H, Oshima, M, Masuko, T, Wright, NA, Furuhashi, S, Hirashima, K, Baba, H, Kitagawa, Y, Saya, H & Nagano, O 2013, 'Functional role of CD44v-xCT system in the development of spasmolytic polypeptide-expressing metaplasia', Cancer Science, vol. 104, no. 10, pp. 1323-1329. https://doi.org/10.1111/cas.12236
Wada, Takeyuki ; Ishimoto, Takatsugu ; Seishima, Ryo ; Tsuchihashi, Kenji ; Yoshikawa, Momoko ; Oshima, Hiroko ; Oshima, Masanobu ; Masuko, Takashi ; Wright, Nicholas A. ; Furuhashi, Satoshi ; Hirashima, Kotaro ; Baba, Hideo ; Kitagawa, Yuko ; Saya, Hideyuki ; Nagano, Osamu. / Functional role of CD44v-xCT system in the development of spasmolytic polypeptide-expressing metaplasia. In: Cancer Science. 2013 ; Vol. 104, No. 10. pp. 1323-1329.
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