Abstract
Circulating tumor cells (CTC) are newly discovered biomarkers of cancers. Although many systems detect CTC, a gold standard has not yet been established. We analyzed CTC in uterine cervical cancer patients using an advanced version of conditionally replicative adenovirus targeting telomerase-positive cells, which was enabled to infect coxsackievirus-adenovirus receptor-negative cells and to reduce false-positive signals in myeloid cells. Blood samples from cervical cancer patients were hemolyzed and infected with the virus and then labeled with fluorescent anti-CD45 and anti-pan cytokeratin antibodies. GFP (+)/CD45 (−) cells were isolated and subjected to whole-genome amplification followed by polymerase chain reaction analysis of human papillomavirus (HPV) DNA. CTC were detected in 6 of 23 patients with cervical cancers (26.0%). Expression of CTC did not correlate with the stage of cancer or other clinicopathological factors. In 5 of the 6 CTC-positive cases, the same subtype of HPV DNA as that of the corresponding primary lesion was detected, indicating that the CTC originated from HPV-infected cancer cells. These CTC were all negative for cytokeratins. The CTC detected by our system were genetically confirmed. CTC derived from uterine cervical cancers had lost epithelial characteristics, indicating that epithelial marker-dependent systems do not have the capacity to detect these cells in cervical cancer patients.
| Original language | English |
|---|---|
| Pages (from-to) | 231-240 |
| Number of pages | 10 |
| Journal | Cancer Science |
| Volume | 109 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 1 2018 |
Fingerprint
Keywords
- cervical cancer
- circulating tumor cell
- cytokeratin
- human papilloma virus
- telomerase
ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
Detection of circulating tumor cells in cervical cancer using a conditionally replicative adenovirus targeting telomerase-positive cells. / Takakura, Masahiro; Matsumoto, Takeo; Nakamura, Mitsuhiro; Mizumoto, Yasunari; Myojyo, Subaru; Yamazaki, Rena; Iwadare, Jyunpei; Bono, Yukiko; Orisaka, Shunsuke; Obata, Takeshi; Iizuka, Takashi; Kagami, Kyosuke; Nakayama, Kentaro; Hayakawa, Hideki; Sakurai, Fuminori; Mizuguchi, Hiroyuki; Urata, Yasuo; Fujiwara, Toshiyoshi; Kyo, Satoru; Sasagawa, Toshiyuki; Fujiwara, Hiroshi.
In: Cancer Science, Vol. 109, No. 1, 01.01.2018, p. 231-240.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Detection of circulating tumor cells in cervical cancer using a conditionally replicative adenovirus targeting telomerase-positive cells
AU - Takakura, Masahiro
AU - Matsumoto, Takeo
AU - Nakamura, Mitsuhiro
AU - Mizumoto, Yasunari
AU - Myojyo, Subaru
AU - Yamazaki, Rena
AU - Iwadare, Jyunpei
AU - Bono, Yukiko
AU - Orisaka, Shunsuke
AU - Obata, Takeshi
AU - Iizuka, Takashi
AU - Kagami, Kyosuke
AU - Nakayama, Kentaro
AU - Hayakawa, Hideki
AU - Sakurai, Fuminori
AU - Mizuguchi, Hiroyuki
AU - Urata, Yasuo
AU - Fujiwara, Toshiyoshi
AU - Kyo, Satoru
AU - Sasagawa, Toshiyuki
AU - Fujiwara, Hiroshi
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Circulating tumor cells (CTC) are newly discovered biomarkers of cancers. Although many systems detect CTC, a gold standard has not yet been established. We analyzed CTC in uterine cervical cancer patients using an advanced version of conditionally replicative adenovirus targeting telomerase-positive cells, which was enabled to infect coxsackievirus-adenovirus receptor-negative cells and to reduce false-positive signals in myeloid cells. Blood samples from cervical cancer patients were hemolyzed and infected with the virus and then labeled with fluorescent anti-CD45 and anti-pan cytokeratin antibodies. GFP (+)/CD45 (−) cells were isolated and subjected to whole-genome amplification followed by polymerase chain reaction analysis of human papillomavirus (HPV) DNA. CTC were detected in 6 of 23 patients with cervical cancers (26.0%). Expression of CTC did not correlate with the stage of cancer or other clinicopathological factors. In 5 of the 6 CTC-positive cases, the same subtype of HPV DNA as that of the corresponding primary lesion was detected, indicating that the CTC originated from HPV-infected cancer cells. These CTC were all negative for cytokeratins. The CTC detected by our system were genetically confirmed. CTC derived from uterine cervical cancers had lost epithelial characteristics, indicating that epithelial marker-dependent systems do not have the capacity to detect these cells in cervical cancer patients.
AB - Circulating tumor cells (CTC) are newly discovered biomarkers of cancers. Although many systems detect CTC, a gold standard has not yet been established. We analyzed CTC in uterine cervical cancer patients using an advanced version of conditionally replicative adenovirus targeting telomerase-positive cells, which was enabled to infect coxsackievirus-adenovirus receptor-negative cells and to reduce false-positive signals in myeloid cells. Blood samples from cervical cancer patients were hemolyzed and infected with the virus and then labeled with fluorescent anti-CD45 and anti-pan cytokeratin antibodies. GFP (+)/CD45 (−) cells were isolated and subjected to whole-genome amplification followed by polymerase chain reaction analysis of human papillomavirus (HPV) DNA. CTC were detected in 6 of 23 patients with cervical cancers (26.0%). Expression of CTC did not correlate with the stage of cancer or other clinicopathological factors. In 5 of the 6 CTC-positive cases, the same subtype of HPV DNA as that of the corresponding primary lesion was detected, indicating that the CTC originated from HPV-infected cancer cells. These CTC were all negative for cytokeratins. The CTC detected by our system were genetically confirmed. CTC derived from uterine cervical cancers had lost epithelial characteristics, indicating that epithelial marker-dependent systems do not have the capacity to detect these cells in cervical cancer patients.
KW - cervical cancer
KW - circulating tumor cell
KW - cytokeratin
KW - human papilloma virus
KW - telomerase
UR - http://www.scopus.com/inward/record.url?scp=85040701785&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85040701785&partnerID=8YFLogxK
U2 - 10.1111/cas.13449
DO - 10.1111/cas.13449
M3 - Article
C2 - 29151279
AN - SCOPUS:85040701785
VL - 109
SP - 231
EP - 240
JO - Cancer Science
JF - Cancer Science
SN - 1347-9032
IS - 1
ER -