Expression of phosphorylated-STAT3 and osteopontin and their correlation in melanoma

Abstract

The expressions of p-STAT3 and osteopontin in 22 cases of normal nevi and 43 cases of malignant melanoma were immunohistochemically detected, and the correlation between p-STAT3 and osteopontin in malignant melanoma and the correlations of p-STAT3 (or osteopontin) with invasion, metastasis and thickness of malignant melanoma were examined. The results showed p-STAT3 was expressed in 2 of 22 cases of normal nevi and 30 of 43 cases of malignant melanoma, while osteopontin was expressed in 3 cases of normal nevi and 29 cases of malignant melanoma. The expressions of p-STAT3 and osteopontin in melanoma were significantly higher than that in benign nevi. There existed significant correlations between the expression of p-STAT3 and that of osteopontin in melanoma. Furthermore, the expression rates of p-STAT3 were significantly higher in invasive or metastatic melanomas than that their non-invasive or non-metastatic counterparts, and the expression rates of osteopontin were significantly higher in invasive melanomas than that in non-invasive ones. It is concluded that p-STAT3 and osteopontin may play important roles in the pathogenesis of malignant melanoma.

Keywords

p-STAT3 / osteopontin / malignant melanoma / invasion / metastasis / tumor thickness

References

[1] LiY., Mc ClayE.F.. Systemic chemotherapy for the treatment of metastatic melanoma. Semin Oncol, 2002, 29: 413-426

[2] SuiqingC., MinZ., LirongC.. Overexpression of phosphorylated-STAT3 correlated with the invasion and metastasis of cutaneous squamous cell carcinoma. J Dermatol, 2005, 32: 354-360

[3] YangS.F., YuanS.S., YehY.T., et al. . The role of p-STAT3 (ser727) revealed by its association with Ki-67 in cervical intraepithelial neoplasia. Gynecol Oncol, 2005, 98: 446-452

[4] YangS.F., WangS.N., WuC.F., et al. . Altered p-STAT3 (tyr705) expression is associated with histological grading and intratumour microvessel density in hepatocellular carcinoma. J Clin Pathol, 2007, 60: 642-648

[5] CoppolaD., SzaboM., BoulwareD., et al. . Correlation of osteopontin protein expression and pathological stage across a wide variety of tumor histologies. Clin Cancer Res, 2004, 10: 184-190

[6] WaiP.Y., KuoP.C.. The role of Osteopontin in tumor metastasis. J Surg Res, 2004, 121: 228-241

[7] DenhardtD.T., MistrettaD., ChambersA.F., et al. . Transcriptional regulation of osteopontin and the metastatic phenotype: evidence for a Ras-activated enhancer in the human OPN promoter. Clin Exp Metastasis, 2003, 20: 77-84

[8] BalchC.M., BuzaidA.C., SoongS.J., et al. . Final version of the American Joint Committee on Cancer system for cutaneous melanoma. J Clin Oncol, 2001, 19: 3635-3648

[9] HorvathC.M.. STAT proteins and transcriptional responses to extracellular signals. TIBS, 2000, 25: 496-502

[10] HeimbergerA.B., PriebeW.. Small molecular inhibitors of p-STAT3: novel agents for treatment of primary and metastatic CNS cancers. Recent Pat CNS Drug Discov, 2008, 3: 179-188

[11] KortylewskiM., JoveR., YuH.. Targeting STAT3 affects melanoma on multiple fronts. Cancer and Metastasis Reviews, 2005, 24: 315-327

[12] ChakrabortyG., JainS., BeheraR., et al. . The multifaceted roles of osteopontin in cell signaling, tumor progression and angiogenesis. Curr Mol Med, 2006, 6: 819-830

[13] SengerD.R., PerruzziC.A., PapadopoulosA.. Elevated expression of secreted phosphoprotein I (osteopontin, 2ar) as a consequence of neoplastic transformation. Anticancer Res, 1989, 9(5): 1291-1299

[14] PhilipS., BulbuleA., KunduG.C.. Osteopontin stimulates tumor growth and activation of promatrix metalloproteinase-2 through nuclear factor-k B-mediated induction of membrane type I matrix metalloproteinase in murine melanoma cells. J Biol Chem, 2001, 276: 44926-44935

[15] RangaswamiH., KunduG.C.. Osteopontin stimulates melanoma growth and lung metastasis through NIK/MEKK1-dependent MMP-9 activation pathways. Oncol Rep, 2007, 18: 909-915

[16] ShijuboN., UedeT., KonS., et al. . Vascular endothelial growth factor and osteopontin in tumor biology. Crit Rev Oncog, 2000, 11(2): 135-146

[17] XieT.X., WeiD., LiuM., et al. . Stat3 activation regulates the expression of matrix metalloproteinase-2 and tumor invasion and metastasis. Oncogene, 2004, 23: 3550-3560

[18] SatoshiL., CynthiaD.B., GaryE.G., et al. . Inhibition of Src kinase activity by ad-mda7 suppresses vascular endothelial growth factor expression in prostate carcinoma cells. Mol Ther, 2005, 12: 707-715

[19] SengerD.R., LedbetterS.R., ClaffeyK.P., et al. . Stimulation of endo-thelial cell migration by vascular permeability fac-tor/vascular endothelial growth factor through cooperative mechanisms involving the avh3 integrin, osteopontin, and thrombin. Am J Pathol, 1996, 149: 293-305

[20] ChakrabortyG., JainS., KunduG.C.. Osteopontin promotes vascular endothelial growth factor-dependent breast tumor growth and angiogenesis via autocrine and paracrine mechanisms. Cancer Res, 2008, 68(1): 152-161