Chimeric Mouse model to track the migration of bone marrow derived cells in glioblastoma following anti-angiogenic treatments

B. R. Achyut, Adarsh Shankar, A. S M Iskander, Roxan Ara, Robert A. Knight, Alfonso G. Scicli, Ali S. Arbab

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Bone marrow derived cells (BMDCs) have been shown to contribute in the tumor development. In vivo animal models to investigate the role of BMDCs in tumor development are poorly explored. We established a novel chimeric mouse model using as low as 5 × 10(6) GFP+ BM cells in athymic nude mice, which resulted in >70% engraftment within 14 d. In addition, chimera was established in NOD-SCID mice, which displayed >70% with in 28 d. Since anti-angiogenic therapies (AAT) were used as an adjuvant against VEGF-VEGFR pathway to normalize blood vessels in glioblastoma (GBM), which resulted into marked hypoxia and recruited BMDCs to the tumor microenvironment (TME). We exploited chimeric mice in athymic nude background to develop orthotopic U251 tumor and tested receptor tyrosine kinase inhibitors and CXCR4 antagonist against GBM. We were able to track GFP+ BMDCs in the tumor brain using highly sensitive multispectral optical imaging instrument. Increased tumor growth associated with the infiltration of GFP+ BMDCs acquiring suppressive myeloid and endothelial phenotypes was seen in TME following treatments. Immunofluorescence study showed GFP+ cells accumulated at the site of VEGF, SDF1 and PDGF expression, and at the periphery of the tumors following treatments. In conclusion, we developed a preclinical chimeric model of GBM and phenotypes of tumor infiltrated BMDCs were investigated in context of AATs. Chimeric mouse model could be used to study detailed cellular and molecular mechanisms of interaction of BMDCs and TME in cancer.

Original languageEnglish (US)
Pages (from-to)280-90
Number of pages11
JournalCancer Biology and Therapy
Volume17
Issue number3
DOIs
StatePublished - 2016

Fingerprint

Glioblastoma
Bone Marrow Cells
Tumor Microenvironment
Neoplasms
Nude Mice
Vascular Endothelial Growth Factor A
Therapeutics
Phenotype
Cellular Microenvironment
Inbred NOD Mouse
SCID Mice
Optical Imaging
Receptor Protein-Tyrosine Kinases
Brain Neoplasms
Fluorescent Antibody Technique
Blood Vessels
Animal Models
Growth

Keywords

  • Bone marrow
  • Glioblastoma
  • microenvironment
  • resistance
  • tumor angiogenesis
  • VEGF

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Molecular Medicine
  • Pharmacology

Cite this

Chimeric Mouse model to track the migration of bone marrow derived cells in glioblastoma following anti-angiogenic treatments. / Achyut, B. R.; Shankar, Adarsh; Iskander, A. S M; Ara, Roxan; Knight, Robert A.; Scicli, Alfonso G.; Arbab, Ali S.

In: Cancer Biology and Therapy, Vol. 17, No. 3, 2016, p. 280-90.

Research output: Contribution to journalArticle

Achyut, B. R. ; Shankar, Adarsh ; Iskander, A. S M ; Ara, Roxan ; Knight, Robert A. ; Scicli, Alfonso G. ; Arbab, Ali S. / Chimeric Mouse model to track the migration of bone marrow derived cells in glioblastoma following anti-angiogenic treatments. In: Cancer Biology and Therapy. 2016 ; Vol. 17, No. 3. pp. 280-90.
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