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Dependence of autocrine growth factor stimulation in platelet‐derived growth factor‐B‐induced mouse brain tumor cells
Author(s) -
Uhrbom Lene,
Hesselager Göran,
Östman Arne,
Nistér Monica,
Westermark Bengt
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(20000201)85:3<398::aid-ijc17>3.0.co;2-l
Subject(s) - autocrine signalling , platelet derived growth factor receptor , platelet derived growth factor , biology , growth factor , chondroitin sulfate proteoglycan , cancer research , paracrine signalling , tyrosine kinase , microbiology and biotechnology , receptor , endocrinology , signal transduction , proteoglycan , biochemistry , extracellular matrix
In human gliomas, platelet‐derived growth factor (PDGF) ligand and receptor mRNA are often co‐expressed, which suggests the presence of an autocrine loop. To further investigate the significance of PDGF stimulation in brain tumors, we used a previously developed mouse tumor model, in which malignant brain tumors of neuroepithelial origin were induced by injecting a murine retrovirus containing the human PDGF B‐chain gene into the brains of neonatal mice. In the present investigation, we have characterized a cell line established from such an experimentally induced tumor in an INK4a ‐/‐ mouse. Cultured tumor cells expressed nestin and NG2 chondroitin sulfate proteoglycan and are thus most likely derived from an oligodendrocyte precursor cell. Tumor cells produced PDGF‐B protein and displayed constitutively activated PDGF α receptors. Autocrine receptor activation could be blocked with the specific PDGF receptor tyrosine kinase inhibitor CGP 57148B, which led to almost complete inhibition of cell proliferation, which was much less affected by a PDGF B‐chain aptamer that inhibits binding of PDGF‐B to PDGF receptors and is unlikely to be able to pass through the plasma membrane. Our results imply an important role for PDGF autocrine stimulation in both initiation and progression of a subtype of gliomas. Int. J. Cancer 83:398–406, 2000. ©2000 Wiley‐Liss, Inc.