Hematopoietic stem and progenitor cell migration after hypofractionated radiation therapy in a murine model

Jonathan Kane, Sarah A. Krueger, Joshua T. Dilworth, John T. Torma, George D. Wilson, Brian Marples, Gerard J. Madlambayan

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1162-1170
Number of pages9
JournalInternational Journal of Radiation Oncology Biology Physics
Volume87
Issue number5
DOIs
StatePublished - Dec 1 2013
Externally publishedYes

Fingerprint

stem cells
Hematopoietic Stem Cells
Cell Movement
radiation therapy
Radiotherapy
tumors
stems
cells
bone marrow
Neoplasms
tomography
irradiation
mice
positrons
Bone Marrow
cytometry
staining
radiation
Radiation
Lewis Lung Carcinoma

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation
  • Cancer Research
  • Medicine(all)

Cite this

Hematopoietic stem and progenitor cell migration after hypofractionated radiation therapy in a murine model. / Kane, Jonathan; Krueger, Sarah A.; Dilworth, Joshua T.; Torma, John T.; Wilson, George D.; Marples, Brian; Madlambayan, Gerard J.

In: International Journal of Radiation Oncology Biology Physics, Vol. 87, No. 5, 01.12.2013, p. 1162-1170.

Research output: Contribution to journalArticle

Kane, Jonathan ; Krueger, Sarah A. ; Dilworth, Joshua T. ; Torma, John T. ; Wilson, George D. ; Marples, Brian ; Madlambayan, Gerard J. / Hematopoietic stem and progenitor cell migration after hypofractionated radiation therapy in a murine model. In: International Journal of Radiation Oncology Biology Physics. 2013 ; Vol. 87, No. 5. pp. 1162-1170.
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