Skip to main content


Log in

Albumin fusion with human lactoferrin shows enhanced inhibition of cancer cell migration

  • Published:
BioMetals Aims and scope Submit manuscript


The fusion of human serum albumin (HSA) with human lactoferrin (hLF) (designated as hLF-HSA) has improved the pharmacokinetic properties and anti-proliferative activities of hLF against cancer cells. In this study, we evaluated the anti-migratory activities of hLF and hLF-HSA against the human lung adenocarcinoma PC-14 cell line using wound healing and Boyden chamber assays. Despite the unexpected hLF-induced migration, hLF-HSA clearly demonstrated the complete inhibition of PC-14 cell migration. To examine the mechanism underlying the enhanced PC-14 cell migration by hLF alone but suppressed migration by hLF-HSA, we focused on the matrix metalloproteinase (MMP) family of endopeptidases because MMPs are often reported to play important roles in facilitating the migration and metastasis of cancer cells. Furthermore, hLF is a transactivator of MMP1 transcription. As expected, treatment of cells with hLF and hLF-HSA led to the upregulation and downregulation of MMP1, respectively. In contrast, MMP9 expression levels, which are often associated with cancer migration, were unchanged in the presence of either protein. An MMP inhibitor attenuated hLF-induced migration of PC-14 cells. Therefore, specific enhancement and suppression of MMP1 expression by hLF and hLF-HSA have been implicated as causes of a marked increase and decrease in PC-14 cell migration, respectively. In conclusion, the fusion of HSA with hLF (hLF-HSA) promoted its anti-migratory effects against cancer cells. Therefore, hLF-HSA is a promising anti-cancer drug candidate based on its improved anti-migratory activity towards cancer cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others


Download references


The authors thank Hiroto Ishida (School of Bioscience and Biotechnology, Tokyo University of Technology) for providing technical assistance. We are grateful to Prof. Yuko Murakami (School of Bioscience and Biotechnology, Tokyo University of Technology), Dr. Misa Imai (Graduate School of Medicine, Juntendo University, Tokyo, Japan), and Dr. Masao Nakamura (Sasaki Institute, Sasaki Foundation, Tokyo, Japan) for their useful discussions.


This research did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations



HN: investigation, writing, review, and editing. DK: investigation and review. AS: conceptualization, writing, reviewing, editing, and supervision. All authors reviewed the manuscript.

Corresponding author

Correspondence to Atsushi Sato.

Ethics declarations

Conflict of interest

A. Sato was the founder of S&K Biopharma Inc. (Kawasaki, Kanagawa, Japan).

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nopia, H., Kurimoto, D. & Sato, A. Albumin fusion with human lactoferrin shows enhanced inhibition of cancer cell migration. Biometals 36, 629–638 (2023).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: