Platelet-derived growth factor (PDGF) in neoplastic and non-neoplastic cystic lesions of the central nervous system and in the cerebrospinal fluid

Abstract

Summary The aim of this study was to determine the concentration of PDGF in vivo in neoplastic and non-neoplastic brain lesions. Fluid from cystic lesions and cerebrospinal fluid was tested in a radioreceptor assay that detects all described PDGF isoforms. High concentrations of PDGF were found in cyst fluids from several astrocytomas, one metastatic melanoma, one metastatic lung adenocarcinoma and one intracerebral abscess. The PDGF concentrations were several times higher than the levels known to be required for maximal PDGF effects on cells in vitro. PDGF could also be detected in some non-neoplastic lesions, especially one intracerebral abscess. The finding of high amounts of PDGF in neoplastic lesions strongly supports the possibility that PDGF can be a mediator of tumour and stromal cell growth and motility in vivo. Comparison of PDGF and P-thromboglobulin concentrations in the same fluids strongly indicates that the PDGF protein is locally produced rather than a result of platelet activation and derangement of the blood-brain barrier.

Platelet-derived Growth Factor Induces a Long-term Inhibition of -Methyl-D-aspartate Receptor Function

“…PDGF, like the neurothrophins, is 1) produced locally and is important for the development, differentiation, proliferation, and survival of neuronal and glial cells (7,10,11,17); 2) coupled to tyrosine kinase receptors that activate complex intracellular signaling pathways (2); and 3) released as part of the compensatory response to central nervous system injury or disease (13,15,16). We now report that PDGF exerts another function that is characteristic of the neurotrophic factors, which is the modulation of neurotransmitter receptors in the central nervous system (29).…”

“…Elevations of PDGF levels in the central nervous system have been detected during neurological diseases associated with excitotoxicity and neuronal death such as infections, trauma, and cerebrovascular ischemic disease (13,15,16). Therefore, the inhibitory actions of PDGF on NMDA-R function could also be important in the pathophysiology of these conditions because a decrease in Ca 2ϩ influx through NMDA-Rs should help to restore homeostasis and prevent cell death.…”

“…Cell lines from malignant glioma and other central nervous system tumors express PDGFs and PDGFRs, and it has been suggested that growth of some of these tumors could be mediated by an autocrine PDGF/PDGFR loop (13,14). Moreover, PDGF levels are elevated in non-neoplastic diseases of the central nervous system such as trauma, stroke, meningitis, cerebral abscesses, and glial and meningeal cysts (13,15,16). It is likely that this elevation in PDGF levels is involved not only in the pathogenesis of these conditions but also in the tissue repair processes associated with these diseases.…”

Migration of human glioma cells in response to tumour cyst fluids

“…In fact, plasma proteins constitute a major fraction of gliomatous cyst fluids [20,31]. At least for PDGF in human glioma cysts Nister et al [25] were able to demonstrate by comparison of PDGF and platelet derived ~-thromboglobulin concentrations that PDGF in those cysts was most probably not derived from haematopoetic cells. PDGF has been implicated in the control of glioma proliferation and invasion in an autocrine loop fashion [34].…”

“…The mechanisms of cyst formation suggest that cyst fluids may accumulate a variety of tumour cell produced soluble factors or factors released by normal reactive brain cells within tumour tissue or within the cyst walls. In fact, tumour cell growth promoting activity has been identified in glioma cyst fluids in experimental model systems [28,37] and subsequently different authors have demonstrated several growth factors such as PDGF, aFGF, VEGF, as well as somatomedins contained in cyst fluids of gliomas [24,25,29,35].…”