Overexpression of the natural tetrapeptide acetyl-N-ser-asp-lys-pro derived from thymosin beta 4 in neoplastic diseases

International audienceThe natural tetrapeptide acetyl-ser-asp-lys-pro (AcSDKP) is formed in vivo by enzymatic cleavage of the N terminus of thymosin beta4 by prolyl oligopeptidase (POP). Recently, AcSDKP was shown to promote angiogenesis. Because of the critical role of neovascularization in cancer development, the levels of AcSDKP and POP activity in a number of different malignant tissues were investigated. Our studies revealed that AcSDKP levels were markedly elevated in neoplastic diseases including hematologic malignancies and solid neoplasms. Consistent with this finding, the enhanced activity of POP was also detected in all analyzed specimens of cancer tissues. Both these novel findings are in concert with the previously reported overexpression of thymosin beta4 in a large variety of malignant tumors and with its potential role in cancerogenesis. The physiological relevance of these findings awaits further studies; however, our first results strongly suggest a key role for AcSDKP in the pathogenesis of cancer

Overexpression of the Angiogenic Tetrapeptide AcSDKP in Human Malignant Tumors

Background: The natural tetrapeptide acetyl-SerAsp-Lys-Pro (AcSDKP), generated from thymosin beta 4 following its cleavage by prolyl oligopeptidase (POP), is a physiological stimulator of angiogenesis. Because of the critical role of neovascularisation in tumor development, the expression of AcSDKP and the activity of POP were examined in different human solid malignancies. Materials and Methods: The expression of AcSDKP and the activity of POP were evaluated in human blood samples and tissue specimens of thyroid goiter and thyroid papillary carcinoma as well as in commercial cancer tissue microarray. Results: A significantly increased concentration of AcSDKP in intratumoral blood and enhanced tissular activity of POP were detected in cancer patients. The expression of AcSDKP in human breast, colon, head and neck, kidney, lung, skin, ovary and prostate cancer tissues was shown to be greater than that in normal tissues. Conclusion: AcSDKP and POP contribute to the malignant phenotype and these molecules are potentiel markers of cancer