ADAM12 peptide

Aim: In this prospective monocenter study, the authors aimed to investigate the correlations between levels of serum human disintegrin and metalloproteinase domain-containing protein 12 (ADAM12), pregnancy-associated plasma protein A (PAPP-A), serum-free beta hCG (f beta-hCG), and baby birth weights in two groups of pregnant women whose risks for trisomy 21 was found higher and lower than threshold value in first trimester screening test. Materials and Methods: Seventy-nine pregnant women were included the study. Using first trimester screening test, 40 of them were categorized as having above threshold risk (1/250) for trisomy 21 and, 39 of them were below threshold risk. ELISA method was used to measure the levels of serum ADAM12 and chemiluminescence method was used to measure the levels of PAPP-A and f beta-hCG. Results: In pregnant women at risk, ADAM12, PAPP-A multiple of median (MoM), and baby birth weights were found significantly lower than control group (p < 0.001, p < 0.001, and p = 0.029, respectively) while the levels of f beta-hCG MoM were higher than those of control group (p < 0.001). In the group of pregnant women having low birth weight (LBW) babies, ADAM12 levels were found lower than the group having normal birth weight babies (NBW) (p < 0.033). Also, the values of f beta-hCG MoM were found higher in comparison to NBW group (p < 0.029). A positive significant correlation was observed between ADAM12 concentrations and PAPP-A MoM (r = 0.630). Conclusions: Maternal serum ADAM12 levels are useful as biomarkers which support other screening parameters for predicting trisomy 21 risk. Additionally, maternal serum ADAM12 levels could be used for prediction of baby birth weights.

A Disintegrin and Metalloproteinase 12 (ADAM12) is expressed significantly higher in multiple tumors than in normal tissues and has been used as a prognostic marker for the evaluation of cancer progression. Although several ADAM12 substrates have been identified biochemically and its proteolytic function has been explored, the upstream regulators and the interacting proteins have not been systematically investigated. Here, we use immunoprecipitation and mass spectrometry (MS)-based quantitative proteomic approaches to identify 28 interacting partners for the long form of ADAM12 (ADAM12-L) in HeLa cells. Proteins that regulate cell proliferation, invasion, and epithelial to mesenchymal transition are among the identified ADAM12-interacting proteins. Further biochemical experiments discover that the protein level and the stability of ADAM12 are upregulated by one of its interacting proteins, myoferlin. In addition, myoferlin also increases the proteolytic activity of ADAM12, leading to the reduction of an ADAM12 substrate, E-cadherin. This result implies that ADAM12 and its interacting proteins might converge to certain signaling pathways in the regulation of cancer cell progression. The information obtained here might be useful in the development of new strategies for modulating cell proliferation and invasion involved in the regulation between ADAM12 and its interacting partners. MS data are available via ProteomeXchange with identifier PXD003560. Biological significance: Regulation of the proliferation and invasion of cancer cells is important in cancer treatment. ADAM12 has been found to play important roles in regulating these processes and identification of its interacting partners will improve our understanding of its biological functions and provide basis for functional modulation. Through mass spectrometry-based quantitative proteomic approaches, we identify the interacting partners for ADAM12 in a human cancer cell line and find many proteins that are involved in the proliferation and invasion of cancer cells. A novel regulator, myoferlin, of ADAM12 is discovered and this protein increases ADAM12 expression level, stability, and its enzymatic activity, leading to the reduction of its substrate, E-cadherin, which plays important roles in the regulation of cell adhesion and tumor metastasis. This result provides a connection for two highly expressed proteins in cancer cells and may shed light on the regulation of their biological functions in cancer progression. (C) 2016 Elsevier B.V. All rights reserved.