Ras/Raf/MEK/ERK pathway is associated with lung metastasis of osteosarcoma in an orthotopic mouse model.

AIM

To identify a marker of osteosarcoma metastasis and to inhibit the marker against the invasive ability of an osteosarcoma cell line (143B).

MATERIALS AND METHODS

Type I insulin-like growth factor receptor (IGF-1R) and its downstream signalling factors were measured in samples from our orthotopic 143B mouse model by immunohistochemistry. A Matrigel assay was used to assess cell invasion ability under interference.

RESULTS

All 15 mice had tumour mass at the left tibia. Total IGF-1R, MEK, Akt, p38 and phosphorylated MEK (p-MEK), but not p-Akt and p-p38, were positive in both local tumours and lung secondaries. Leiomyosarcoma controls expressed p-Akt and p-MEK, but not p-p38. The 143B cells treated with U0126, a MEK/ERK inhibitor, had significantly lower in vitro invasion ability compared with controls.

CONCLUSION

The IGF-1R-MEK signalling pathway, particularly Ras/Raf/MEK/ERK, may play an important role in osteosarcoma lung metastasis, and the targeting MEK/ERK by its specific inhibitor may have a potential use in the effective treatment of osteosarcoma.