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 language | English |
|---|---|
| Pages (from-to) | 1110-1119 |
| Number of pages | 10 |
| Journal | Annals of Surgical Oncology |
| Volume | 24 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 1 2017 |
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All Science Journal Classification (ASJC) codes
- Surgery
- Oncology
Cite this
Identification and Characterization of CD107a as a Marker of Low Reactive Oxygen Species in Chemoresistant Cells in Colorectal Cancer. / Kitahara, Tomohiro; Haraguchi, Naotsugu; Takahashi, Hidekazu; Nishimura, Junichi; Hata, Taishi; Takemasa, Ichiro; Mizushima, Tsunekazu; Yamamoto, Hirofumi; Doki, Yuichiro; Mori, Masaki.
In: Annals of Surgical Oncology, Vol. 24, No. 4, 01.04.2017, p. 1110-1119.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Identification and Characterization of CD107a as a Marker of Low Reactive Oxygen Species in Chemoresistant Cells in Colorectal Cancer
AU - Kitahara, Tomohiro
AU - Haraguchi, Naotsugu
AU - Takahashi, Hidekazu
AU - Nishimura, Junichi
AU - Hata, Taishi
AU - Takemasa, Ichiro
AU - Mizushima, Tsunekazu
AU - Yamamoto, Hirofumi
AU - Doki, Yuichiro
AU - Mori, Masaki
PY - 2017/4/1
Y1 - 2017/4/1
N2 - 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.
AB - 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.
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U2 - 10.1245/s10434-016-5671-8
DO - 10.1245/s10434-016-5671-8
M3 - Article
C2 - 27834032
AN - SCOPUS:84994783005
VL - 24
SP - 1110
EP - 1119
JO - Annals of Surgical Oncology
JF - Annals of Surgical Oncology
SN - 1068-9265
IS - 4
ER -