Identification and Characterization of CD107a as a Marker of Low Reactive Oxygen Species in Chemoresistant Cells in Colorectal Cancer

Tomohiro Kitahara, Naotsugu Haraguchi, Hidekazu Takahashi, Junichi Nishimura, Taishi Hata, Ichiro Takemasa, Tsunekazu Mizushima, Hirofumi Yamamoto, Yuichiro Doki, Masaki Mori

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Reactive oxygen species (ROS) generated by chemoradiotherapy lead to cancer cell death. Although ROS regulation mechanisms play important roles in chemoradioresistance, few markers exist that indicated intracellular ROS status. This study aimed to identify novel cell surface markers that represented intracellular ROS status to characterize cells with low ROS (ROSlow) in colorectal cancer (CRC). Methods: We used ROS indicators and an antibody array with 242 cell surface antibodies to identify markers of ROSlow cells. After validation, we performed immunohistochemical analyses and chemosensitivity assays. We used small interfering RNA to assess the effect of silencing the identified markers. We tested cell differentiation assays with spheroid cell assays. Results: CD107a was identified as a common marker of ROSlow cells in several CRC cell lines and clinical specimens. CD107a+/ROSlow cells were enriched in HT29 and DLD1 cultures after treatments with oxaliplatin, 5-fluorouracil, and the irinotecan metabolite SN38. CD107a silencing improved chemosensitivity by increasing ROS production. Immunohistochemistry showed enhanced CD107a surface expression on cells that formed immature cell clusters and on cells located in the invasive fronts of cancer foci. CD107a expression was also enhanced on specimens from patients with poorly differentiated adenocarcinoma who had received neoadjuvant chemotherapy. Cell surface CD107a expression was enhanced on cells that formed colonospheres, but expression diminished during cell differentiation. Conclusions: CD107a was identified as a novel marker of ROSlow cells in CRC. CD107a expression was closely related to chemoresistance and the immature cell phenotype. Anti-CD107a treatments represent a novel approach for targeting chemoresistant cells in CRC.

Original languageEnglish
Pages (from-to)1110-1119
Number of pages10
JournalAnnals of Surgical Oncology
Volume24
Issue number4
DOIs
Publication statusPublished - Apr 1 2017
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

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