Platelet‐derived growth factor is mitogenic for O‐2A^adult progenitor cells

Abstract

We report that platelet-derived growth factor (PDGF) is a potent mitogen for oligodendrocyte type-2 astrocyte (O-2A) progenitor cells derived from the optic nerves of adult rats. Moreover, O-2Aadult progenitors cultured in PDGF express the range of properties we have described previously for O-2Aadult progenitors cultured in the presence of type-1 astrocytes. Similarly, previous studies have demonstrated that PDGF is able to mimic the influence of type-1 astrocytes on O-2Aperinatal progenitors. Specifically, O-2Aadult progenitors and O-2Aperinatal progenitors exposed to PDGF express differences in average cell cycle time (59 +/- 5 h for O-2Aadult progenitors versus 20 +/- 6 h for O-2Aperinatal progenitors), average rate of migration (4.1 +/- 0.6 microns h-1 versus 24.6 +/- 5.4 microns h-1), morphology (unipolar versus bipolar), and antigenic phenotype (04+ vimentin- versus 04- vimentin+). Thus, our present results indicate that a single signalling molecule secreted by type-1 astrocytes produces markedly different cellular behaviours in two related O-2A progenitor populations.

Glial Progenitors in Adult White Matter Are Driven to Form Malignant Gliomas by Platelet-Derived Growth Factor-Expressing Retroviruses

“…In contrast, neonatal progenitors are highly migratory and proliferative and resemble glioma cells in their capacity to infiltrate long distances through brain tissue Kakita and Goldman, 1999;Suzuki and Goldman, 2003). However, in vitro studies have shown that adult glial progenitors can be induced to become more migratory and proliferative when treated with growth factors including PDGF, basic fibroblast growth factor, and glial growth factor (Wolswijk et al, 1991;Wolswijk and Noble, 1992;Shi et al, 1998). Our results provide the first in vivo evidence that PDGF can drive adult glial progenitors to acquire a more migratory and proliferative behavior.…”

“…(2) Many human gliomas express markers also expressed by glial progenitors, including olig2, NG2, and PDGF receptor ␣ (PDGFR␣), suggesting a close relationship (Shoshan et al, 1999;Chekenya and Pilkington, 2002;Bouvier et al, 2003;Ligon et al, 2004). (3) PDGF is a powerful mitogen for both glioma cells and adult glial progenitors (Wolswijk et al, 1991;Wolswijk and Noble, 1992;Vassbotn et al, 1994). (4) Human gliomas often express both PDGF and its receptor, suggesting that autocrine and paracrine PDGF signaling plays a role in glioma growth and progression (Hermanson et al, 1992;Westermark et al, 1995;Di Rocco et al, 1998).…”

Adult brain retains the potential to generate oligodendroglial progenitors with extensive myelination capacity

“…However, that all of the cells were positive for vimentin and A2B5 but negative for O4 contrasts with the antigenic phenotype of the O2A adult as isolated directly from adult rat optic nerves (9). More importantly, the oligosphere cells proliferate much more vigorously and differentiate and migrate faster than the O2A adult progenitors detailed in a series of studies performed by Noble and colleagues (9,(28)(29)(30). Therefore, the OPs from adult neural precursor cells resemble neonatal rather than adult O2As isolated directly BrdUrdϩ cells and total cells were counted in four optic fields of each coverslip.…”

Malignant glioma: genetics and biology of a grave matter

“…Perhaps PDGF's most important role in the low-grade tumors may be to induce tumor cell migration through activation of PI3-K and PLC-␥, both of which have been implicated in migration and scattering (Heldin 1996;Willis et al 2000). Although PDGF's role in smooth muscle cell, fibroblast, and oligodendrocyte migration is well established (Wolswijk et al 1991;Bilato et al 1995;Milner et al 1997;Facchiano et al 2000), its role in modulating astrocyte migration is less well defined and therefore merits further investigation. Indeed, cell culture studies have revealed the capacity of PDGF to stimulate migration of oligodendrocyte progenitor cells (Simpson and Armstrong 1999), neonatal rat cortical astrocytes (Bressler et al 1985), and embryonic rat neural stem cells (Forsberg-Nilsson et al 1998).…”