Cold plasma and inhibition of STAT3 selectively target tumorigenicity in osteosarcoma
Por:
Tornin, J, Mateu-Sanz, M, Rey, V, Murillo, D, Huergo, C, Gallego, B, Rodriguez, A, Rodriguez, R and Canal-Barnils C
Publicada:
1 jun 2023
Ahead of Print:
1 mar 2023
Resumen:
Osteosarcoma (OS) is a malignant type of bone cancer that arises in periods of increased bone formation. Curative strategies for these types of tumors have remained essentially unchanged for decades and the overall survival for most advanced cases is still dismally low. This is in part due to the existence of drug resistant Cancer Stem Cells (CSC) with progenitor properties that are responsible for tumor relapse and metastasis. In the quest for therapeutic alternatives for OS, Cold Atmospheric Plasmas and Plasma-Treated Liquids (PTL) have come to the limelight as a source of Reactive Oxygen and Nitrogen Species displaying selectivity towards a variety of cancer cell lines. However, their effects on CSC subpopulations and in vivo tumor growth have been barely studied to date. By employing bioengineered 3D tumor models and in vivo assays, here we show that low doses of PTL increase the levels of pro-stemness factors and the self-renewal ability of OS cells, coupled to an enhanced in vivo tumor growth potential. This could have critical implications to the field. By proposing a combined treatment, our results demonstrate that the deleterious pro-stemness signals mediated by PTL can be abrogated when this is combined with the STAT3 inhibitor S3I-201, resulting in a strong suppression of in vivo tumor growth. Overall, our study unveils an undesirable stem cell-promoting function of PTL in cancer and supports the use of combinatorial strategies with STAT3 inhibitors as an efficient treatment for OS avoiding critical side effects. We anticipate our work to be a starting point for wider studies using relevant 3D tumor models to evaluate the effects of plasma-based therapies on tumor subpopulations of different cancer types. Furthermore, combination with STAT3 inhibition or other suitable cancer type-specific targets can be relevant to consolidate the development of the field.
Filiaciones:
Tornin, J:
BarcelonaTech UPC, EEBE, Mat Sci & Engn Dept, Biomat Biomech & Tissue Engn Grp, C Eduard Maristany 14, Barcelona 08019, Spain
BarcelonaTech UPC, EEBE, Biomed Engn Res Ctr, C Eduard Maristany 14, Barcelona 08019, Spain
UPC, Barcelona Res Ctr Multiscale Sci & Engn, Barcelona 08019, Spain
Inst Recerca St Joan Deu, Barcelona 08034, Spain
Hosp Univ Cent Asturias, Sarcomas & Expt Therapeut Lab, Inst Invest Sanitaria Principado Asturias ISPA, Ave Roma S-N, Oviedo 33011, Spain
Inst Univ Oncol Principado Asturias, Oviedo 33011, Spain
Mateu-Sanz, M:
BarcelonaTech UPC, EEBE, Mat Sci & Engn Dept, Biomat Biomech & Tissue Engn Grp, C Eduard Maristany 14, Barcelona 08019, Spain
BarcelonaTech UPC, EEBE, Biomed Engn Res Ctr, C Eduard Maristany 14, Barcelona 08019, Spain
UPC, Barcelona Res Ctr Multiscale Sci & Engn, Barcelona 08019, Spain
Inst Recerca St Joan Deu, Barcelona 08034, Spain
Rey, V:
Hosp Univ Cent Asturias, Sarcomas & Expt Therapeut Lab, Inst Invest Sanitaria Principado Asturias ISPA, Ave Roma S-N, Oviedo 33011, Spain
Inst Univ Oncol Principado Asturias, Oviedo 33011, Spain
CIBER Oncol CIBERONC, Madrid 28029, Spain
Murillo, D:
Hosp Univ Cent Asturias, Sarcomas & Expt Therapeut Lab, Inst Invest Sanitaria Principado Asturias ISPA, Ave Roma S-N, Oviedo 33011, Spain
Inst Univ Oncol Principado Asturias, Oviedo 33011, Spain
Huergo, C:
Hosp Univ Cent Asturias, Sarcomas & Expt Therapeut Lab, Inst Invest Sanitaria Principado Asturias ISPA, Ave Roma S-N, Oviedo 33011, Spain
Inst Univ Oncol Principado Asturias, Oviedo 33011, Spain
CIBER Oncol CIBERONC, Madrid 28029, Spain
Gallego, B:
Hosp Univ Cent Asturias, Sarcomas & Expt Therapeut Lab, Inst Invest Sanitaria Principado Asturias ISPA, Ave Roma S-N, Oviedo 33011, Spain
Inst Univ Oncol Principado Asturias, Oviedo 33011, Spain
Rodriguez, A:
Hosp Univ Cent Asturias, Sarcomas & Expt Therapeut Lab, Inst Invest Sanitaria Principado Asturias ISPA, Ave Roma S-N, Oviedo 33011, Spain
Inst Univ Oncol Principado Asturias, Oviedo 33011, Spain
Rodriguez, R:
Hosp Univ Cent Asturias, Sarcomas & Expt Therapeut Lab, Inst Invest Sanitaria Principado Asturias ISPA, Ave Roma S-N, Oviedo 33011, Spain
Inst Univ Oncol Principado Asturias, Oviedo 33011, Spain
CIBER Oncol CIBERONC, Madrid 28029, Spain
Canal-Barnils C:
BarcelonaTech UPC, EEBE, Mat Sci & Engn Dept, Biomat Biomech & Tissue Engn Grp, C Eduard Maristany 14, Barcelona 08019, Spain
BarcelonaTech UPC, EEBE, Biomed Engn Res Ctr, C Eduard Maristany 14, Barcelona 08019, Spain
UPC, Barcelona Res Ctr Multiscale Sci & Engn, Barcelona 08019, Spain
Inst Recerca St Joan Deu, Barcelona 08034, Spain
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