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Mascarenhas et al. J Cancer Metastasis Treat 2020;6:23 Journal of Cancer
DOI: 10.20517/2394-4722.2020.52 Metastasis and Treatment

Original Article Open Access

Lobe-specific modulation of B16MET melanoma
lung metastases by nephrilin peptide

Desmond D. Mascarenhas , Puja Ravikumar , Edward P. Amento 3
3
1,2
1 Mayflower Organization for Research & Education, Sunnyvale, CA 94085, USA.
2 Transporin, Inc., Sunnyvale, CA 94085, USA.
3 Molecular Medicine Research Institute, Sunnyvale, CA 94085, USA.

Correspondence to: Desmond D. Mascarenhas, Ph.D., Mayflower Organization for Research & Education, 428 Oakmead Pkwy,
Sunnyvale, CA 94085, USA. E-mail: desmond@transporin.com
How to cite this article: Mascarenhas DD, Ravikumar P, Amento EP. Lobe-specific modulation of B16MET melanoma lung
metastases by nephrilin peptide. J Cancer Metastasis Treat 2020;6:23. http://dx.doi.org/10.20517/2394-4722.2020.52
Received: 17 May 2020 First Decision: 24 Jun 2020 Revised: 24 Jun 2020 Accepted: 06 Jul 2020 Published: 30 Jul 2020

Academic Editor: Rafat A. Siddiqui Copy Editor: Cai-Hong Wang Production Editor: Jing Yu

Abstract
Aim: Nephrilin peptide modulates systemic immune responses to trauma in contexts characterized by
simultaneous inflammation and immunosuppression. This study explores the possibility that nephrilin
peptide may modulate lung metastasis, which also occurs in an environment of concurrent inflammation and
immunosuppression.

Methods: B16MET melanoma cells were injected via the tail vein of mice and the development of lung metastases
was recorded in animals treated with nephrilin peptide or vehicle by subcutaneous bolus injection daily for three
weeks. In a separate experiment, nephrilin was administered by subcutaneous bolus injection for seven days to
study the biodistribution of peptide and possible changes to plasma cytokine levels.

Results: Nephrilin significantly suppressed B16MET lung metastases. Suppression was more effective in deep lobes
with the poorest access to circulation: accessory > inferior > middle > superior. In a separate biodistribution study
in mice, nephrilin showed similar biodistribution levels in kidney, liver, brain, and left lung, but significantly higher
accumulation in the lobes of the right lung in a gradient that matched its effectiveness in suppressing metastases
(accessory > inferior > middle). The latter environments were also characterized by significantly higher local
concentrations of succinate, a proxy for lower levels of oxygenation.

Conclusion: Nephrilin accumulates preferentially in the deep lobes of the right lung in mice and inhibits B16MET
right lung metastases in a lobe-specific manner.

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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