The Exposure to Human Breast Cancer Cells Altered 14 Post-Translational Modifications of Human Serum Albumin.

Abstract

Purpose:

Serum albumin is in contact with practically all cells in the human body, including tumor cells in cancer patients. The purpose of this study was to explore whether cancer cells affect post-translational modifications (PTMs) of albumin.

Material and methods:

Mass spectrometry was used to identify the PTMs. Purified human serum albumin was incubated with human breast cancer cells MDA-MB-231, MDA-MB-468, MCF7, or kept in water or in cell culture media. PTMs which were affected upon exposure of the albumin to cancer cells were identified. Three-dimensional analysis was performed to locate PTMs in albumin.

Results:

We report here that an exposure to human breast cancer cells affected post-translational modifications (PTMs) of 14 peptides of human serum albumin (HSA). PTMs at 8 peptides were observed upon exposure of HSA to metastatic MDA-MB-231 and MDA-MB-468 breast cancer cells. PTMs at another 6 peptides were lost in MDA-MB-231 and MDA-MB-468 cells, while these 6 PTMs were observed in HSA exposed to conditionally tumorigenic MCF7 cells, or in HSA kept in water or a cell culture medium. Cancer cell altered phosphorylation, deamidation followed by methylation, acetylation, myristylation, palmitoylation, methylation, cysteine persulfide, and S-6-FMN cysteine modifications were detected in HSA. These PTMs locate predominantly in IB and IIA domains of HSA. Three-dimensional analysis showed that this region corresponds to the lipid-binding site and Sudlow's site 1.

Conclusion:

Data reported here show that 14 PTMs of human serum albumin can be modified upon its exposure to human breast cancer cells.

• Authors: Surya Kannan, Serhiy Souchelnytskyi
• Journal: EJIFCC (EJIFCC) Vol. 33 Issue 4 Pg. 295-308 (Dec 2022) ISSN: 1650-3414 [Electronic] Italy
• PMID: 36605305 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). All rights reserved.