Cisplatin-Resistant CD44+ Lung Cancer Cells Are Sensitive to Auger Electrons

Karina Lindbøg Madsen; Oke Gerke; Poul F. Høilund-carlsen; Birgitte Brinkmann Olsen

doi:10.3390/ijms23137131

Cisplatin-Resistant CD44⁺ Lung Cancer Cells Are Sensitive to Auger Electrons

Karina Lindbøg Madsen
, Oke Gerke
, Poul F. Høilund-carlsen
, Birgitte Brinkmann Olsen^*

^*Kontaktforfatter

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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Abstract

Cancer stem cells (CSCs) are resistant to conventional therapy and present a major clinical challenge since they are responsible for the relapse of many cancers, including non-small cell lung cancer (NSCLC). Hence, future successful therapy should also eradicate CSCs. Auger electrons have demonstrated promising therapeutic potential and can induce DNA damage while sparing surrounding cells. Here, we sort primary patient-derived NSCLC cells based on their expression of the CSC-marker CD44 and investigate the effects of cisplatin and a thymidine analog (deoxyuridine) labeled with an Auger electron emitter (¹²⁵I). We show that the CD44⁺ populations are more resistant to cisplatin than the CD44⁻ populations. Interestingly, incubation with the thymidine analog 5-[¹²⁵I]iodo-2′-deoxyuridine ([¹²⁵I]I-UdR) induces equal DNA damage, G2/M cell cycle arrest, and apoptosis in the CD44⁻ and CD44⁺ populations. Our results suggest that Auger electron emitters can also eradicate resistant lung cancer CD44⁺ populations.

Originalsprog	Engelsk
Artikelnummer	7131
Tidsskrift	International Journal of Molecular Sciences
Vol/bind	23
Udgave nummer	13
Antal sider	16
ISSN	1422-0067
DOI	https://doi.org/10.3390/ijms23137131
Status	Udgivet - 1. jul. 2022

Bibliografisk note

Funding Information:
This research was funded by The Independent Research Fund Denmark, Technology and Production (grant no. 7017-00303), Director Emil C. Hertz and wife Inger Hertz’ Foundation, Frode Nygaards Foundation, Simon Fougner Hartmanns family Foundation, Einar Willumsens Memorial Foundation, Odense University Hospital Research Council, Eva and Henry Fraenkels Memorial Foundation, Aase and Ejnar Danielsen’s Foundation, Brdr. Hartmann Foundation, Karen S. Jensens Foundation, the Hede Nielsen family Foundation, and Desirée and Niels Ydes Foundation.The authors thank Consultant Karen Ege Olsen, Department of Pathology, Odense University Hospital (Odense, Denmark) and Professor Peter Bjørn Licht, Department of Thoracic, Cardiac and Vascular Surgery, Odense University Hospital (Odense, Denmark) for recruiting the patients.

Funding Information:
Funding: This research was funded by The Independent Research Fund Denmark, Technology and Production (grant no. 7017‐00303), Director Emil C. Hertz and wife Inger Hertz’ Foundation, Frode Nygaards Foundation, Simon Fougner Hartmanns family Foundation, Einar Willumsens Memorial Foundation, Odense University Hospital Research Council, Eva and Henry Fraenkels Memorial Foundation, Aase and Ejnar Danielsen’s Foundation, Brdr. Hartmann Foundation, Karen S. Jensens Foundation, the Hede Nielsen family Foundation, and Desirée and Niels Ydes Foundation.

Finansiering

This research was funded by The Independent Research Fund Denmark, Technology and Production (grant no. 7017-00303), Director Emil C. Hertz and wife Inger Hertz’ Foundation, Frode Nygaards Foundation, Simon Fougner Hartmanns family Foundation, Einar Willumsens Memorial Foundation, Odense University Hospital Research Council, Eva and Henry Fraenkels Memorial Foundation, Aase and Ejnar Danielsen’s Foundation, Brdr. Hartmann Foundation, Karen S. Jensens Foundation, the Hede Nielsen family Foundation, and Desirée and Niels Ydes Foundation.The authors thank Consultant Karen Ege Olsen, Department of Pathology, Odense University Hospital (Odense, Denmark) and Professor Peter Bjørn Licht, Department of Thoracic, Cardiac and Vascular Surgery, Odense University Hospital (Odense, Denmark) for recruiting the patients. Funding: This research was funded by The Independent Research Fund Denmark, Technology and Production (grant no. 7017‐00303), Director Emil C. Hertz and wife Inger Hertz’ Foundation, Frode Nygaards Foundation, Simon Fougner Hartmanns family Foundation, Einar Willumsens Memorial Foundation, Odense University Hospital Research Council, Eva and Henry Fraenkels Memorial Foundation, Aase and Ejnar Danielsen’s Foundation, Brdr. Hartmann Foundation, Karen S. Jensens Foundation, the Hede Nielsen family Foundation, and Desirée and Niels Ydes Foundation.

Dokumenter og links

10.3390/ijms23137131Licens: CC BY

Open Access VersionForlagets udgivne version, 3,68 MBLicens: CC BY

SDU link

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1 Ph.d.-afhandling

Cancer stem cells are sensitive to Auger electron therapy
Madsen, K. L., 11. apr. 2023, Syddansk Universitet. Det Sundhedsvidenskabelige Fakultet. 138 s.
Publikation: Afhandling › Ph.d.-afhandling

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Citationsformater

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title = "Cisplatin-Resistant CD44+ Lung Cancer Cells Are Sensitive to Auger Electrons",

abstract = "Cancer stem cells (CSCs) are resistant to conventional therapy and present a major clinical challenge since they are responsible for the relapse of many cancers, including non-small cell lung cancer (NSCLC). Hence, future successful therapy should also eradicate CSCs. Auger electrons have demonstrated promising therapeutic potential and can induce DNA damage while sparing surrounding cells. Here, we sort primary patient-derived NSCLC cells based on their expression of the CSC-marker CD44 and investigate the effects of cisplatin and a thymidine analog (deoxyuridine) labeled with an Auger electron emitter (125I). We show that the CD44+ populations are more resistant to cisplatin than the CD44− populations. Interestingly, incubation with the thymidine analog 5-[125I]iodo-2′-deoxyuridine ([125I]I-UdR) induces equal DNA damage, G2/M cell cycle arrest, and apoptosis in the CD44− and CD44+ populations. Our results suggest that Auger electron emitters can also eradicate resistant lung cancer CD44+ populations.",

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AB - Cancer stem cells (CSCs) are resistant to conventional therapy and present a major clinical challenge since they are responsible for the relapse of many cancers, including non-small cell lung cancer (NSCLC). Hence, future successful therapy should also eradicate CSCs. Auger electrons have demonstrated promising therapeutic potential and can induce DNA damage while sparing surrounding cells. Here, we sort primary patient-derived NSCLC cells based on their expression of the CSC-marker CD44 and investigate the effects of cisplatin and a thymidine analog (deoxyuridine) labeled with an Auger electron emitter (125I). We show that the CD44+ populations are more resistant to cisplatin than the CD44− populations. Interestingly, incubation with the thymidine analog 5-[125I]iodo-2′-deoxyuridine ([125I]I-UdR) induces equal DNA damage, G2/M cell cycle arrest, and apoptosis in the CD44− and CD44+ populations. Our results suggest that Auger electron emitters can also eradicate resistant lung cancer CD44+ populations.

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