TY - JOUR
T1 - Targeting stanniocalcin-1-expressing tumor cells elicits efficient antitumor effects in a mouse model of human lung cancer
AU - Abe, Kotaro
AU - Kanehira, Masahiko
AU - Ohkouchi, Shinya
AU - Kumata, Sakiko
AU - Suzuki, Yamato
AU - Oishi, Hisashi
AU - Noda, Masafumi
AU - Sakurada, Akira
AU - Miyauchi, Eisaku
AU - Fujiwara, Tohru
AU - Harigae, Hideo
AU - Okada, Yoshinori
N1 - Funding Information:
The authors thank Dr. Hiroyuki Mizuguchi for kindly providing a vector pHMCMV9, and thank Masako Honda for providing pathological specimens, and thank FASTEK, Ltd. and Enago (www.enago.jp) for English language review. This work was supported, in part, by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (18K08167) (Tokyo, Japan), and The Clinical Research Promotion Program for Young Investigators of Tohoku University Hospital. The authors have no competing financial interest related to the work described herein.
Funding Information:
The authors thank Dr. Hiroyuki Mizuguchi for kindly providing a vector pHMCMV9, and thank Masako Honda for providing pathological specimens, and thank FASTEK, Ltd. and Enago ( www.enago.jp ) for English language review. This work was supported, in part, by a Grant‐in‐Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (18K08167) (Tokyo, Japan), and The Clinical Research Promotion Program for Young Investigators of Tohoku University Hospital. The authors have no competing financial interest related to the work described herein.
Publisher Copyright:
© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
PY - 2021/5
Y1 - 2021/5
N2 - Lung cancer is the most common cause of cancer-related death in developed countries; therefore, the generation of effective targeted therapeutic regimens is essential. Recently, gene therapy approaches toward malignant cells have emerged as attractive molecular therapeutics. Previous studies have indicated that stanniocalcin-1 (STC-1), a hormone involved in calcium and phosphate homeostasis, positively regulates proliferation, apoptosis resistance, and glucose metabolism in lung cancer cell lines. In this study, we investigated if targeting STC-1 in tumor cells could be a promising strategy for lung cancer gene therapy. We confirmed that STC-1 levels in peripheral blood were higher in lung cancer patients than in healthy donors and that STC-1 expression was observed in five out of eight lung cancer cell lines. A vector expressing a suicide gene, uracil phosphoribosyltransferase (UPRT), under the control of the STC-1 promoter, was constructed (pPSTC-1-UPRT) and transfected into three STC-1-positive cell lines, PC-9, A549, and H1299. When stably transfected, we observed significant cell growth inhibition using 5-fluorouracil (5-FU) treatment. Furthermore, growth of the STC-1-negative lung cancer cell line, LK-2 was significantly arrested when combined with STC-1-positive cells transfected with pPSTC-1-UPRT. We believe that conferring cytotoxicity in STC-1-positive lung cancer cells using a suicide gene may be a useful therapeutic strategy for lung cancer.
AB - Lung cancer is the most common cause of cancer-related death in developed countries; therefore, the generation of effective targeted therapeutic regimens is essential. Recently, gene therapy approaches toward malignant cells have emerged as attractive molecular therapeutics. Previous studies have indicated that stanniocalcin-1 (STC-1), a hormone involved in calcium and phosphate homeostasis, positively regulates proliferation, apoptosis resistance, and glucose metabolism in lung cancer cell lines. In this study, we investigated if targeting STC-1 in tumor cells could be a promising strategy for lung cancer gene therapy. We confirmed that STC-1 levels in peripheral blood were higher in lung cancer patients than in healthy donors and that STC-1 expression was observed in five out of eight lung cancer cell lines. A vector expressing a suicide gene, uracil phosphoribosyltransferase (UPRT), under the control of the STC-1 promoter, was constructed (pPSTC-1-UPRT) and transfected into three STC-1-positive cell lines, PC-9, A549, and H1299. When stably transfected, we observed significant cell growth inhibition using 5-fluorouracil (5-FU) treatment. Furthermore, growth of the STC-1-negative lung cancer cell line, LK-2 was significantly arrested when combined with STC-1-positive cells transfected with pPSTC-1-UPRT. We believe that conferring cytotoxicity in STC-1-positive lung cancer cells using a suicide gene may be a useful therapeutic strategy for lung cancer.
KW - bystander effect
KW - lung cancer
KW - stanniocalsin-1 (STC-1)
KW - suicide gene
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U2 - 10.1002/cam4.3852
DO - 10.1002/cam4.3852
M3 - Article
C2 - 33826244
AN - SCOPUS:85103648188
VL - 10
SP - 3085
EP - 3100
JO - Cancer Medicine
JF - Cancer Medicine
SN - 2045-7634
IS - 9
ER -