Integrated transcriptomic and glycomic profiling of glioma stem cell xenografts

Norelle C. Wildburger, Shiyue Zhou, Lauren G. Zacharias, Roger A. Kroes, Joseph R. Moskal, Mary Schmidt, Parvin Mirzaei, Joy Gumin, Frederick F. Lang, Yehia Mechref, Carol L. Nilsson

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Bone marrow-derived human mesenchymal stem cells (BM-hMSCs) have the innate ability to migrate or home toward and engraft in tumors such as glioblastoma (GBM). Because of this unique property of BM-hMSCs, we have explored their use for cell-mediated therapeutic delivery for the advancement of GBM treatment. Extravasation, the process by which blood-borne cells - such as BM-hMSCs - enter the tissue, is a highly complex process but is heavily dependent upon glycosylation for glycan-glycan and glycan-protein adhesion between the cell and endothelium. However, in a translationally significant preclinical glioma stem cell xenograft (GSCX) model of GBM, BM-hMSCs demonstrate unequal tropism toward these tumors. We hypothesized that there may be differences in the glycan compositions between the GSCXs that elicit homing ("attractors") and those that do not ("non-attractors") that facilitate or impede the engraftment of BM-hMSCs in the tumor. In this study, glycotranscriptomic analysis revealed significant heterogeneity within the attractor phenotype and the enrichment of high mannose type N-glycan biosynthesis in the non-attractor phenotype. Orthogonal validation with topical PNGase F deglycosylation on the tumor regions of xenograft tissue, followed by nLC-ESI-MS, confirmed the presence of increased high mannose type N-glycans in the non-attractors. Additional evidence provided by our glycomic study revealed the prevalence of terminal sialic acid-containing N-glycans in non-attractors and terminal galactose and N-acetyl-glucosamine N-glycans in attractors. Our results provide the first evidence for differential glycomic profiles in attractor and non-attractor GSCXs and extend the scope of molecular determinates in BM-hMSC homing to glioma.

Original languageEnglish (US)
Pages (from-to)3932-3939
Number of pages8
JournalJournal of Proteome Research
Volume14
Issue number9
DOIs
StatePublished - Sep 4 2015

Fingerprint

Glycomics
Stem cells
Heterografts
Glioma
Polysaccharides
Stem Cells
Mesenchymal Stromal Cells
Bone
Bone Marrow
Tumors
Glioblastoma
Mannose
Neoplasms
Tissue
Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase
Glycosylation
Phenotype
Tropism
Glucosamine
Biosynthesis

Keywords

  • bone marrow-derived human mesenchymal stem cells (BM-hMSCs)
  • glioblastoma
  • glycomics
  • high-mannose
  • N-linked glycosylation
  • sialic acid
  • transcriptomics

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Cite this

Wildburger, N. C., Zhou, S., Zacharias, L. G., Kroes, R. A., Moskal, J. R., Schmidt, M., ... Nilsson, C. L. (2015). Integrated transcriptomic and glycomic profiling of glioma stem cell xenografts. Journal of Proteome Research, 14(9), 3932-3939. https://doi.org/10.1021/acs.jproteome.5b00549

Integrated transcriptomic and glycomic profiling of glioma stem cell xenografts. / Wildburger, Norelle C.; Zhou, Shiyue; Zacharias, Lauren G.; Kroes, Roger A.; Moskal, Joseph R.; Schmidt, Mary; Mirzaei, Parvin; Gumin, Joy; Lang, Frederick F.; Mechref, Yehia; Nilsson, Carol L.

In: Journal of Proteome Research, Vol. 14, No. 9, 04.09.2015, p. 3932-3939.

Research output: Contribution to journalArticle

Wildburger, NC, Zhou, S, Zacharias, LG, Kroes, RA, Moskal, JR, Schmidt, M, Mirzaei, P, Gumin, J, Lang, FF, Mechref, Y & Nilsson, CL 2015, 'Integrated transcriptomic and glycomic profiling of glioma stem cell xenografts', Journal of Proteome Research, vol. 14, no. 9, pp. 3932-3939. https://doi.org/10.1021/acs.jproteome.5b00549
Wildburger NC, Zhou S, Zacharias LG, Kroes RA, Moskal JR, Schmidt M et al. Integrated transcriptomic and glycomic profiling of glioma stem cell xenografts. Journal of Proteome Research. 2015 Sep 4;14(9):3932-3939. https://doi.org/10.1021/acs.jproteome.5b00549
Wildburger, Norelle C. ; Zhou, Shiyue ; Zacharias, Lauren G. ; Kroes, Roger A. ; Moskal, Joseph R. ; Schmidt, Mary ; Mirzaei, Parvin ; Gumin, Joy ; Lang, Frederick F. ; Mechref, Yehia ; Nilsson, Carol L. / Integrated transcriptomic and glycomic profiling of glioma stem cell xenografts. In: Journal of Proteome Research. 2015 ; Vol. 14, No. 9. pp. 3932-3939.
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