Evidence for an association of high levels of endogenous Acetyl-Ser-Asp-Lys-Pro, a potent mediator of angiogenesis, with acute myeloid leukemia development

Abstract

Evidence from clinical and laboratory studies suggests that angiogenesis is important in the progression of solid tumours and hematologic malignancies. We have shown that the naturally occurring tetrapeptide Acetyl-Ser-Asp-Lys-Pro (AcSDKP) is a potent angiogenic factor normally present at nanomolar concentrations in the blood. A murine leukemia model was used to assess whether there was a correlation between levels of endogenous AcSDKP and the development of disease. Levels of AcSDKP in the plasma and bone marrow (BM) cells from mice bearing an acute myeloid leukemia (AML) were five- to ten-fold greater than those in non-leukemic mice. Furthermore, a strong correlation between the concentration of endogenous AcSDKP and the progression of AML was demonstrated. These results are consistent with the marked increase in BM vascularity observed in leukemic mice. The physiologic relevance of these findings awaits further studies and the contribution of AcSDKP to the pathogenesis of leukemia is under investigation.

Preventive and therapeutic effects of thymosin β4 N-terminal fragment Ac-SDKP in the bleomycin model of pulmonary fibrosis

“…daily vs bi-weekly) at a higher dosage could not only block but also reverse the pathologic process. However, considering the potential role of Ac-SDKP in some malignancies [26–29], even though controversial [30], caution should be used to determine whether Ac-SDKP can be harmful in a subset of patients. Nevertheless we must seriously consider the potential therapeutic utilization of Ac-SDKP against pulmonary fibrosis.…”

Prolyl Endopeptidase Activity Is Correlated with Colorectal Cancer Prognosis

“…Assays in cell cultures and in animal models show that some of its natural substrates, like angiotensins and thymosin β4, are implicated in cell growth, angiogenesis and apoptosis 23, 37, 38. Some authors suggest that potentially coordinated actions of this enzyme with matrix metalloproteinases are at the base of some inflammatory conditions 39, and still others advocate that PEP regulates the angiogenesis and cell growth independently from its catalytic action 17,40,41.…”

N-acetyl-seryl-aspartyl-lysyl-proline: a valuable endogenous anti-fibrotic peptide for combating kidney fibrosis in diabetes

“…The association between tumor angiogenesis and the levels of Tβ4 and AcSDKP has been studied by Wdzieczak-Bakala et al (1990), and these authors have proposed that high levels of Tβ4 and AcSDKP are linked to tumor progression in hematologic malignancies (Liu et al, 2006, 2008, 2009a, 2010). Angiogenesis plays a pivotal role in cancer development (Nyberg et al, 2005; Folkman, 2007), and the AcSDKP level has been shown to be higher in hematologic malignancies and solid neoplasms (Liu et al, 2006, 2008, 2009a, 2010). An association between the AcSDKP level and tumor angiogenesis was observed in these previous studies, but the pathophysiological significance of this result was not clearly shown.…”