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

研究成果: ジャーナルへの寄稿学術論文査読

20 被引用数 (Scopus)


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.

ジャーナルNitric Oxide - Biology and Chemistry
出版ステータス出版済み - 30-04-2015

All Science Journal Classification (ASJC) codes

  • 生化学
  • 生理学
  • 臨床生化学
  • 癌研究


「Impacts of CD44 knockdown in cancer cells on tumor and host metabolic systems revealed by quantitative imaging mass spectrometry」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。