Insulin-like growth factor I stimulates motility in human neuroblastoma cells

Abstract

Motility is an important process that contributes to cancer cell spread. Growth factors are key regulators of motility in many cell types. Insulin-like growth factor I (IGF-I) causes SH-SY5Y human neuroblastoma cells to undergo dynamic morphological changes, leading to the extension of lamellipodia. IGF-I stimulated lamellipodia extension requires signaling through both phosphatidylinositol 3-kinase (PI3-K) and MAP kinase pathways. IGF-I, over a period of hours, stimulates SH-SY5Y and SHEP neuroblastoma cells to become more motile. While SH-SY5Y and SHEP cells use di erent insulin receptor substrate (IRS) isoforms to transduce signals from the IGF-I receptor, IGF-I has the same relative e ect on the motility of both cell lines. Blocking the PI3-K and MAP kinase pathways attenuates the ability of IGF-I to increase motility. Overexpression of PTEN also attenuates IGF-I mediated motility. These results delineate some of the proximal events in the signaling mechanism utilized by IGF-I to stimulate cell motility. Oncogene (2001) 20, 7542 ± 7550.

Insulin-like growth factor-I signaling in human neuroblastoma cells

“…Growth factors, particularly IGF-I and -II, represent one such class of signaling molecules. IGF-I/II signaling through IGF-IR can modulate neuroblastoma survival, differentiation, proliferation and motility (Singleton et al, 1996;Kim et al, 1997;van Golen and Feldman, 2000;Meyer et al, 2001). The current study expands on our previous reports by examining IGF-I signaling in specific neuroblastoma cell types.…”

“…We have previously reported that IGF-I treatment of N cells induces morphological changes accompanied by actin cytoskeletal rearrangement Kim and Feldman, 1998;Kim et al, 1998a) followed by neuronal differentiation . IGF-I treatment also enhances the motility of N and S cells (Meyer et al, 2001). In this report, we extended our previous studies with a more detailed examination of differential IGF-I signaling in N-and Stype neuroblastoma cell lines.…”

“…Previously we have reported that SH-EP cells express IRS-1 and low levels of IGF-IR compared to SH-SY5Y cells, which express higher IGF-IR levels and IRS-2 (Singleton et al, 1996;Meyer et al, 2001). In this report, we extended this study to compare IGF-I signaling in other neuroblastoma cell lines.…”

Insulin receptor substrates mediate distinct biological responses to insulin-like growth factor receptor activation in breast cancer cells

“…Cell motility was measured using a gold particle phagokinetic assay, as previously described (Albrecht-Buehler, 1977;Meyer et al, 2001). Briefly, glass coverslips were pre-coated with 1.5 ml of a 5 mg ml À1 solution of fibronectin in SFM overnight at 41C and then coated with a freshly prepared gold particle solution (10.6 mM sodium carbonate, 12.7 mM gold chloride and 0.0087% formaldehyde) and incubated overnight at 41C to allow the gold particles to precipitate.…”

Rapamycin inhibits cell motility by suppression of mTOR-mediated S6K1 and 4E-BP1 pathways

“…Increasing evidence indicates that IGF-I signaling is also pivotal to cell motility and invasion (LeRoith and Roberts, 2003). For example, activation of IGF-IR and subsequent activation of PI3K and mitogen-activated protein kinase pathways induces motility of neuroblastoma cells (Meyer et al, 2001). By affecting integrin relocation and association of the E-cadherin/catenin complex with the cytoskeleton, IGF-I stimulates migration of epithelial colonic cells (Andre et al, 1999) and myeloma cells (Tai et al, 2003).…”