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Analysis of radiation effects in two irradiated tumor spheroid models
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.ORCID-id: 0000-0002-6771-3289
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
2018 (engelsk)Inngår i: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 15, nr 3, s. 3008-3016Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Multicellular spheroids have proven suitable as three-dimensional in vivo-like models of non-vascularized micrometastases. Unlike monolayer-based models, spheroids mirror the cellular milieu and the pathophysiological gradients inside tumor nodules. However, there is limited knowledge of the radiation effects at the molecular level in spheroids of human origin. The present study is a presentation of selected cell biological processes that may easily be analyzed with methods available at routine pathology laboratories. Using gamma irradiated pancreatic neuroendocrine BON1 and colonic adenocarcinoma HCT116 spheroids as model systems, the present study assessed the radiobiological response in these models. Spheroid growth after irradiation was followed over time and molecular responses were subsequently assessed with immunohistochemistry (IHC) staining for descriptive analyses and semi-automatic grading of apoptosis, G(2)-phase and senescence in thin sections of the spheroids. Growth studies demonstrated the BON1 spheroids were slower growing and less sensitive to radiation compared with the HCT116 spheroids. IHC staining for G2-phase was primarily observed in the outer viable P-cell layers of the spheroids, with the 6 Gy irradiated HCT116 spheroids demonstrating a very clear increase in staining intensity compared with unirradiated spheroids. Apoptosis staining results indicated increased apoptosis with increasing radiation doses. No clear association between senescence and radiation exposure in the spheroids were observed. The present results demonstrate the feasibility of the use of multicellular spheroids of human origin in combination with IHC analyses to unravel radiobiological responses at a molecular level. The present findings inspire further investigations, including other relevant IHC-detectable molecular processes in time-and radiation dose-dependent settings.

sted, utgiver, år, opplag, sider
2018. Vol. 15, nr 3, s. 3008-3016
Emneord [en]
three-dimensional cell culture, spheroids, irradiation, IHC, pancreatic neuroendocrine cancer, colonic adenocarcinoma
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-354258DOI: 10.3892/ol.2017.7716ISI: 000430818300039PubMedID: 29435031OAI: oai:DiVA.org:uu-354258DiVA, id: diva2:1228766
Tilgjengelig fra: 2018-06-28 Laget: 2018-06-28 Sist oppdatert: 2018-06-28bibliografisk kontrollert

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