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Hypoxic jumbo spheroids on-a-chip (HOnAChip): insights into treatment efficacy

Elena Refet-Mollof, Ouafa Najyb, Rodin Chermat, Audrey Glory, Julie Lafontaine, Philip Wong and Thomas Gervais

Article (2021)

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Hypoxia is a key characteristic of the tumor microenvironment, too rarely considered during drug development due to the lack of a user-friendly method to culture naturally hypoxic 3D tumor models. In this study, we used soft lithography to engineer a microfluidic platform allowing the culture of up to 240 naturally hypoxic tumor spheroids within an 80 mm by 82.5 mm chip. These jumbo spheroids on a chip are the largest to date (>750 µm), and express gold-standard hypoxic protein CAIX at their core only, a feature absent from smaller spheroids of the same cell lines. Using histopathology, we investigated response to combined radiotherapy (RT) and hypoxic prodrug Tirapazamine (TPZ) on our jumbo spheroids produced using two sarcoma cell lines (STS117 and SK-LMS-1). Our results demonstrate that TPZ preferentially targets the hypoxic core (STS117: p = 0.0009; SK-LMS-1: p = 0.0038), but the spheroids’ hypoxic core harbored as much DNA damage 24 h after irradiation as normoxic spheroid cells. These results validate our microfluidic device and jumbo spheroids as potent fundamental and pre-clinical tools for the study of hypoxia and its effects on treatment response.

Uncontrolled Keywords

hypoxia; microfluidics; spheroids; tumor microenvironment; CAIX; HIF1-α; radiotherapy; Tirapazamine; sarcoma

Subjects: 1900 Biomedical engineering > 1900 Biomedical engineering
3100 Physics > 3100 Physics
3100 Physics > 3101 Atomic and molecular studies
Department: Department of Engineering Physics
Institut de génie biomédical
Funders: Fonds de Recherche du Québec-Santé, Fonds de Recherche du Québec, TransMedTech Institute - Canada First Research Excellence Fund, The Strategic Training in Transdisciplinary Radiation Science for the 21st Century (STARS21) training program, Institut du Cancer de Montreal and Bourse Canderel
Grant number: 32730, 34612, 262832
PolyPublie URL: https://publications.polymtl.ca/9371/
Journal Title: Cancers (vol. 13, no. 16)
Publisher: MDPI
DOI: 10.3390/cancers13164046
Official URL: https://doi.org/10.3390/cancers13164046
Date Deposited: 16 Aug 2023 12:17
Last Modified: 07 Nov 2023 11:31
Cite in APA 7: Refet-Mollof, E., Najyb, O., Chermat, R., Glory, A., Lafontaine, J., Wong, P., & Gervais, T. (2021). Hypoxic jumbo spheroids on-a-chip (HOnAChip): insights into treatment efficacy. Cancers, 13(16), 20 pages. https://doi.org/10.3390/cancers13164046


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