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Tokyo University of Technology discovers fusion protein of human lactoferrin and human serum albumin is a powerful inhibitor of cancer cell migration


A research group led by Professor Atsushi Sato of the Graduate School of Bionics, Computer and Media Sciences, Tokyo University of Technology, has discovered that a fusion protein of human lactoferrin (hLF) and human serum albumin (HSA) is a powerful inhibitor of the migration of cancer and is closely related to cancer cell metastasis.

Human lactoferrin is a protein with anti-tumor, anti-inflammatory and antioxidant properties that functions as an innate component of the immune system in the human body. Because of its useful biological activity, it is anticipated to be used as a biopharmaceutical.

In previous studies, the research group has found that fusing hLF with HSA, the most abundant protein in blood (hLF-HSA), improves the stability of hLF in the body as well as its growth inhibitory effect on cancer cells.

As such, the research group used genetic recombination technology using CHO cells (Chinese hamster ovary cells) to produce hLF-HSA. Using these cells, they tested their effect on cancer cell migration in a cancer cell migration assay using PC-14, a human lung adenocarcinoma cell line. They found that hLF promoted PC-14 migration. In contrast, hLF-HSA almost completely inhibited PC-14 migration. This effect was not observed when hLF and HSA were added simultaneously, suggesting that the fusion of hLF and HSA is important for the expression of the action.

Effects of various protein additions on PC-14 cell migration (stained areas are migrating cancer cells). The hLF-HSA fusion not only inhibits proliferation to cancer cells, but also strongly inhibits migration.
Provided by Tokyo University of Technology

To further explore this mechanism, the researchers focused analysis on the expression of matrix metalloproteinases (MMP), which promote cancer cell migration and metastasis. In PC-14 cells, hLF treatment increased the expression of MMP-1, while hLF-HSA treatment suppressed it. On the other hand, none of them affected MMP-9 expression. This revealed that the different effects of hLF and hLF-HSA on PC-14 cell migration are due to differential regulation of its expression on MMP-1. This indicates that hLF-HSA may not only inhibit the growth of cancer cells, but also strongly inhibit their migration.

"Recently, we found that hLF-HSA has an even higher therapeutic effect than hF in the same spinal cord injury animal model," commented Sato. "Based on this, we believe that hLF-HSA could be an effective treatment for spinal cord injuries for which there is no proven cure, and we have established a drug discovery venture company (S&K Biopharma) to develop the drug."

Journal Information
Publication: BioMetals
Title: Albumin fusion with human lactoferrin shows enhanced inhibition of cancer cell migration
DOI: 10.1007/s10534-022-00447-9

This article has been translated by JST with permission from The Science News Ltd. ( Unauthorized reproduction of the article and photographs is prohibited.

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