Hematopoietic stem and progenitor cell migration after hypofractionated radiation therapy in a murine model.
Int J Radiat Oncol Biol Phys
; 87(5): 1162-70, 2013 Dec 01.
Article
em En
| MEDLINE
| ID: mdl-24113056
ABSTRACT
PURPOSE:
To characterize the recruitment of bone marrow (BM)-derived hematopoietic stem and progenitor cells (HSPCs) within tumor microenvironment after radiation therapy (RT) in a murine, heterotopic tumor model. METHODS AND MATERIALS Lewis lung carcinoma tumors were established in C57BL/6 mice and irradiated with 30 Gy given as 2 fractions over 2 days. Tumors were imaged with positron emission tomography/computed tomography (PET/CT) and measured daily with digital calipers. The HSPC and myelomonocytic cell content was assessed via immunofluorescent staining and flow cytometry. Functionality of tumor-associated HSPCs was verified in vitro using colony-forming cell assays and in vivo by rescuing lethally irradiated C57BL/6 recipients.RESULTS:
Irradiation significantly reduced tumor volumes and tumor regrowth rates compared with nonirradiated controls. The number of CD133(+) HSPCs present in irradiated tumors was higher than in nonirradiated tumors during all stages of regrowth. CD11b(+) counts were similar. PET/CT imaging and growth rate analysis based on standardized uptake value indicated that HSPC recruitment directly correlated to the extent of regrowth and intratumor cell activity after irradiation. The BM-derived tumor-associated HSPCs successfully formed hematopoietic colonies and engrafted irradiated mice. Finally, targeted treatment with a small animal radiation research platform demonstrated localized HSPC recruitment to defined tumor subsites exposed to radiation.CONCLUSIONS:
Hypofractionated irradiation resulted in a pronounced and targeted recruitment of BM-derived HSPCs, possibly as a mechanism to promote tumor regrowth. These data indicate for the first time that radiation therapy regulates HSPC content within regrowing tumors.
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Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Hematopoéticas
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Movimento Celular
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Carcinoma Pulmonar de Lewis
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Neoplasias Pulmonares
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Recidiva Local de Neoplasia
Limite:
Animals
Idioma:
En
Revista:
Int J Radiat Oncol Biol Phys
Ano de publicação:
2013
Tipo de documento:
Article