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Secretomes reveal several novel proteins as well as TGF-β1 as the top upstream regulator of metastatic process in breast cancer

  • Preclinical study
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

A Correction to this article was published on 02 May 2018

This article has been updated

Abstract

Purpose

Metastatic breast cancer is resistant to many conventional treatments and novel therapeutic targets are needed. We previously isolated subsets of 4T1 murine breast cancer cells which metastasized to liver (4TLM), brain (4TBM), and heart (4THM). Among these cells, 4TLM is the most aggressive one, demonstrating mesenchymal phenotype. Here we compared secreted proteins from 4TLM, 4TBM, and 4THM cells and compared with that of hardly metastatic 67NR cells to detect differentially secreted factors involved in organ-specific metastasis.

Method and results

Label-free LC–MS/MS proteomic technique was used to detect the differentially secreted proteins. Eighty-five of over 500 secreted proteins were significantly altered in metastatic breast cancer cells. Differential expression of several proteins such as fibulin-4, Bone Morphogenetic Protein 1, TGF-β1 MMP-3, MMP-9, and Thymic Stromal Lymphopoietin were further verified using ELISA or Western blotting. Many of these identified proteins were also present in human metastatic breast carcinomas. Annexin A1 and A5, laminin beta 1, Neutral alpha-glucosidase AB were commonly found at least in three out of six studies examined here. Ingenuity Pathway Analysis showed that proteins differentially secreted from metastatic cells are involved primarily in carcinogenesis and TGF-β1 is the top upstream regulator in all metastatic cells.

Conclusions

Cells metastasized to different organs displayed significant differences in several of secreted proteins. Proteins differentially altered were fibronectin, insulin-like growth factor-binding protein 7, and Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1. On the other hand, many exosomal proteins were also common to all metastatic cells, demonstrating involvement of key universal factors in distant metastatic process.

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Change history

  • 02 May 2018

    In the original publication of the article, Acknowledgement section was missed out and Table 1 was published incompletely. The Acknowledgment and complete table 1 are given in this correction. The original article has been corrected.

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Acknowledgements

This study was supported by TUBITAK. Grant No: 115Z286.

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Authors and Affiliations

  1. Department of Medical Pharmacology, School of Medicine, Akdeniz University, B-blok kat 1, SBAUM/Immunoloji Lab, Antalya, Turkey

    Nuray Erin & Nur Ogan

  2. Department of Medical Biology, School of Medicine, Dumlupınar University, Kütahya, Turkey

    Azmi Yerlikaya

Authors
  1. Nuray Erin
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  2. Nur Ogan
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  3. Azmi Yerlikaya
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Corresponding author

Correspondence to Nuray Erin.

Additional information

The original version of this article was revised: In the original publication of the article, Acknowledgement section was missed out and table 1 was published incompletely.

Electronic supplementary material

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Supplementary material 1 (DOC 33 kb)

Supplementary material 2 (PDF 131 kb)

10549_2018_4752_MOESM3_ESM.xls

Supplementary material 3 (XLS 1103 kb). Supplemental Table 1: Total of 1855 peptides mapping to 592 proteins secreted into the conditioned medium. Each colored column represents the peptide scores identified in certain cells. Yellow: 67NR cells, green: 4TBM cells, red: 4TLM cells, orange: 4THM cells.

10549_2018_4752_MOESM4_ESM.xlsx

Supplementary material 4 (XLSX 43 kb). Supplemental Table 2: 224 peptides mapping to 85 different proteins which were significantly altered. Each colored column represent the peptide scores identified in certain cells. Yellow: 67NR cells, green: 4TBM cells, red: 4TLM cells, orange: 4THM cells.

10549_2018_4752_MOESM5_ESM.xls

Supplementary material 5 (XLS 31 kb). Supplemental Table 3: Localization of significantly altered proteins. Data was obtained from Panther.org. Non-exosomal proteins were shown in yellow lines.

10549_2018_4752_MOESM6_ESM.xlsx

Supplementary material 6 (XLSX 42 kb). Supplemental Table 4: List of proteins in our study overlapped with at least two other studies.

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Erin, N., Ogan, N. & Yerlikaya, A. Secretomes reveal several novel proteins as well as TGF-β1 as the top upstream regulator of metastatic process in breast cancer. Breast Cancer Res Treat 170, 235–250 (2018). https://doi.org/10.1007/s10549-018-4752-8

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  • DOI: https://doi.org/10.1007/s10549-018-4752-8

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