Expression of IGF-I and IGF-II Receptors in Rat C6 Glioma Cells as a Function of the Growth Phase

Abstract

In the present study, we examined the specific binding of IGF-I and IGF-II to their receptors in C6 glioma cells taken during different growth phases in culture: phase A, early stage of the exponential growth (48 h after seeding); phase B, late stage of the exponential phase (96 h after seeding); phase C, confluent phase (at 144 h after seeding); and phase D, stopped at 48 h post-confluence. Scatchard analysis revealed higher K_a values for the IGF-IR during the exponential phases (A and B). The affinity of IGF-I for its receptor during the post-confluent phase (D) decreased to about half that at phase A (p < 0.01). Although lower at the later phase (D), the number of binding sites of the IGF-IR in the different tested growth stages in culture (A, B, and C) was not statistically different (p > 0.05). Conversely, the number of binding sites of the IGF-II/mannose-6-phosphate receptor appeared to increase during time in culture. The K_a values of the IGF-II/mannose-6-phosphate receptor decreased significantly during the culture time, phase D showing the largest decrease (50%) as compared with phase A (p < 0.005). These binding data suggest that IGF-I and IGF-II receptors are differentially expressed in rat C6 glioma cells in culture and are a function of the growth phase.

The natural origins of cytostatic compounds used in rhabdomyosarcoma therapy

“…It has been found that IGF1R and its potent ligand IGF2 are widely overexpressed in childhood sarcomas, including RMS. [26][27][28][29][30][31] The activity of IGF1R can be inhibited (via blocking its phosphorylation and downstream signaling) by picropodophyllin (PPP), which is a cyclolignan isolated from Podophyllum species. 32,33 In vitro studies have revealed that PPP significantly blocks ERMS cell activity, especially migration and proliferation.…”

“…Therefore, they are frequent targets in ERMS treatment using doxorubicin, irinotecan, temozolomide, vinblastine, cyclophosphamide, or topotecan. 23,35,37,38 Some in vitro studies have revealed positive effects when combining ERMS therapy with buparlisib (PI3K inhibitor), AEW541 (IGF1R inhibitor) and rapamycin (mTOR adults, very rarely in children [13], [14], [15], [18], [24], [25], [26], [27] s children, adults [11], [16], [17], [18], [28], [29], [30], [31] MyoG -MoD1 myogenin; MSA -muscle-specific actin; SMA -smooth muscle actin; CGH -comparative genomic in situ hybridization; IHC -immunohistochemistry.…”