Platelet-derived growth factor-mediated gliomagenesis and brain tumor recruitment Journal Article
| Authors: | Fomchenko, E. I.; Holland, E. C. |
| Article Title: | Platelet-derived growth factor-mediated gliomagenesis and brain tumor recruitment |
| Abstract: | The roles of various members of the PDGF family during development are mirrored by a variety of functions of PDGFs during gliomagenesis. Elevated transcription and increased protein levels of these growth factors have been correlated with several types of cancer, including gliomas. PDGF overexpression has been shown to be causal in glioma formation in GEMs, regionally variable, and quantitatively correlated with higher grade tumor structures. To some degree, these effects may be attributable to the ability of PDGFs to cause phenotypic dedifferentiation or prevent glial cell differentiation. Activation of signaling pathways downstream of the PDGFRs has been shown to be causal in glioma initiation, whereas activation of other signaling pathways correlated with glioma progression. Similar to normal development, the action of PDGFs during gliomagenesis is not only autocrine but paracrine in nature. PDGF production by glioma cells can stimulate its expressors and recruit other cell types into the tumor. PDGF has been implicated in regulating tumor vasculogenesis mediated by the recruitment of EPCs, pericytes, and vascular smooth muscle cells and in tumor IFP by its effects on tumor stroma. Additionally, brain tumors are known to contain implanted as well as endogenous NSC/PCs attracted to the growth factor-rich glioma environment, migrating in juxtaposition and homing to glioma cells. The realization of the importance of interaction between the brain tumor microenvironment and tumor cells and active recruitment of nonstromal cell types leads to a more complex view of brain tumor formation. Although the popular CSC theory proposes the existence of a clonal brain tumor, the ability of various mutations and PDGF signaling to alter the apparent lineage and differentiation state and extensive paracrine modes of action of PDGF suggest additional nonclonal complexity during gliomagenesis. Although the existence of a normal stromal component may certainly be present in the tumors, the recruitment view of brain tumorigenesis proposes the possibility of nonclonal tumor development mediated by perpetual growth factor stimulation. The recruitment of nontumor cell types and the possibility of mutations arising in the recruited cell population allow for its expansion and alteration of the cellular composition of the tumors. © 2007 Elsevier Inc. All rights reserved. |
| Keywords: | signal transduction; mitogen activated protein kinase; platelet derived growth factor; protein expression; cancer surgery; review; nonhuman; brain tumor; glioma; brain neoplasms; protein function; cell proliferation; animals; imatinib; cell structure; protein protein interaction; neural stem cell; cell differentiation; cell population; protein tyrosine kinase; angiogenesis; phosphatidylinositol 3 kinase; carcinogenesis; cell lineage; gene expression regulation, neoplastic; xenograft; glioma cell; janus kinase; tumor recurrence; tumor cell line; cancer stem cell; platelet-derived growth factor; tumor cell; stem cells; oligodendroglioma; tumor growth; protein structure; mammalian target of rapamycin inhibitor; tumor resistance; gene structure; phospholipase c gamma; intracranial tumor; platelet derived growth factor b; platelet derived growth factor a; platelet derived growth factor c; platelet derived growth factor d; astrocytoma cell |
| Journal Title: | Neurosurgery Clinics of North America |
| Volume: | 18 |
| Issue: | 1 |
| ISSN: | 1042-3680 |
| Publisher: | W.B. Saunders Co-Elsevier Inc. |
| Date Published: | 2007-01-01 |
| Start Page: | 39 |
| End Page: | 58 |
| Language: | English |
| DOI: | 10.1016/j.nec.2006.10.006 |
| PUBMED: | 17244553 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 15" - "Export Date: 17 November 2011" - "CODEN: NCNAF" - "Source: Scopus" |
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