Impacts of CD44 knockdown in cancer cells on tumor and host metabolic systems revealed by quantitative imaging mass spectrometry

Mitsuyo Ohmura, Takako Hishiki, Takehiro Yamamoto, Tsuyoshi Nakanishi, Akiko Kubo, Kenji Tsuchihashi, Mayumi Tamada, Sakino Toue, Yasuaki Kabe, Hideyuki Saya, Makoto Suematsu

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

CD44 expressed in cancer cells was shown to stabilize cystine transporter (xCT) that uptakes cystine and excretes glutamate to supply cysteine as a substrate for reduced glutathione (GSH) for survival. While targeting CD44 serves as a potentially therapeutic stratagem to attack cancer growth and chemoresistance, the impact of CD44 targeting in cancer cells on metabolic systems of tumors and host tissues in vivo remains to be fully determined. This study aimed to reveal effects of CD44 silencing on alterations in energy metabolism and sulfur-containing metabolites in vitro and in vivo using capillary electrophoresis-mass spectrometry and quantitative imaging mass spectrometry (Q-IMS), respectively. In an experimental model of xenograft transplantation of human colon cancer HCT116 cells in superimmunodeficient NOG mice, snap-frozen liver tissues containing metastatic tumors were examined by Q-IMS. As reported previously, short hairpin CD44 RNA interference (shCD44) in cancer cells caused significant regression of tumor growth in the host liver. Under these circumstances, the CD44 knockdown suppressed polyamines, GSH and energy charges not only in metastatic tumors but also in the host liver. In culture, HCT116 cells treated with shCD44 decreased total amounts of methionine-pool metabolites including spermidine and spermine, and reactive cysteine persulfides, suggesting roles of these metabolites for cancer growth. Collectively, these results suggest that CD44 expressed in cancer accounts for a key regulator of metabolic interplay between tumor and the host tissue.

Original languageEnglish
Pages (from-to)102-113
Number of pages12
JournalNitric Oxide - Biology and Chemistry
Volume46
DOIs
Publication statusPublished - 2015 Apr 30

Fingerprint

Mass spectrometry
Tumors
Mass Spectrometry
Cells
Imaging techniques
Metabolites
Liver
Cystine
Neoplasms
Tissue
RNA
Capillary electrophoresis
HCT116 Cells
Spermidine
Spermine
Polyamines
Cell culture
Sulfur
Heterografts
Methionine

Keywords

  • Cancer
  • Polyamines
  • Reactive cysteine persulfides
  • Remethylation
  • Transsulfuration
  • xCT

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Cancer Research
  • Physiology

Cite this

Impacts of CD44 knockdown in cancer cells on tumor and host metabolic systems revealed by quantitative imaging mass spectrometry. / Ohmura, Mitsuyo; Hishiki, Takako; Yamamoto, Takehiro; Nakanishi, Tsuyoshi; Kubo, Akiko; Tsuchihashi, Kenji; Tamada, Mayumi; Toue, Sakino; Kabe, Yasuaki; Saya, Hideyuki; Suematsu, Makoto.

In: Nitric Oxide - Biology and Chemistry, Vol. 46, 30.04.2015, p. 102-113.

Research output: Contribution to journalArticle

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