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Updated: Feb 2, 2026

A Permanent Window for Investigating Cancer Metastasis to the Lung
Published on: July 1, 2021
Newly developed anti-S100A8/A9 monoclonal antibody efficiently prevents lung tropic cancer metastasis
Rie Kinoshita1, Hiroki Sato2, Akira Yamauchi3
1Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Abstract:
The metastatic dissemination of cancer cells to remote areas of the body is the most problematic aspect in cancer patients. Among cancers, melanomas are notoriously difficult to treat due to their significantly high metastatic potential even during early stages. Hence, the establishment of advanced therapeutic approaches to regulate metastasis is required to overcome the melanoma disease. An accumulating mass of evidence has indicated a critical role of extracellular S100A8/A9 in melanoma distant metastasis. Lung S100A8/A9 is induced by melanoma cells from distant organs and it attracts these cells to its enriched lung environment since melanoma cells possess several receptors that sense the S100A8/A9 ligand. We hence aimed to develop a neutralizing antibody against S100A8/A9 that would efficiently block melanoma lung metastasis. Our protocol provided us with one prominent antibody, Ab45 that efficiently suppressed not only S100A8/A9-mediated melanoma mobility but also lung tropic melanoma metastasis in a mouse model. This prompted us to make chimeric Ab45, a chimera antibody consisting of mouse Ab45-Fab and human IgG2-Fc. Chimeric Ab45 also showed significant inhibition of the lung metastasis of melanoma. From these results, we have high hopes that the newly produced antibody will become a potential biological tool to block melanoma metastasis in future clinical settings.
Insights
Researchers developed a new antibody, Ab45, to block melanoma metastasis. This antibody targets S100A8/A9, a protein crucial for cancer cell spread to the lungs, showing promise for future melanoma treatments.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Metastatic dissemination is a primary challenge in cancer treatment, particularly in melanoma due to its high metastatic potential.
- Extracellular S100A8/A9 plays a critical role in promoting melanoma distant metastasis, especially to the lungs.
- Melanoma cells are attracted to the lung environment by S100A8/A9, which they can sense via specific receptors.
Purpose of the Study:
- To develop a neutralizing antibody targeting S100A8/A9 to inhibit melanoma lung metastasis.
- To evaluate the efficacy of a novel antibody (Ab45) and its chimeric form in blocking melanoma cell mobility and metastasis.
Main Methods:
- Development of a neutralizing antibody (Ab45) against extracellular S100A8/A9.
- Testing Ab45's ability to suppress S100A8/A9-mediated melanoma cell mobility in vitro.
- Assessment of Ab45 and its chimeric version (chimeric Ab45) in inhibiting lung tropic melanoma metastasis in a mouse model.
Main Results:
- Ab45 demonstrated significant suppression of S100A8/A9-mediated melanoma cell mobility.
- Both Ab45 and chimeric Ab45 effectively inhibited lung tropic melanoma metastasis in vivo.
- The chimeric antibody, composed of mouse Ab45-Fab and human IgG2-Fc, retained inhibitory activity against melanoma metastasis.
Conclusions:
- A novel antibody, Ab45, and its chimeric form show potential in blocking melanoma lung metastasis.
- Targeting the S100A8/A9 pathway with neutralizing antibodies presents a promising therapeutic strategy for melanoma.
- These antibodies could serve as future biological tools in clinical settings to combat melanoma spread.
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