A novel process for transcellular hemoglobin transport from macrophages to cancer cells
Hemoglobin (Hb) performs its physiological function within the erythrocyte. Extracellular Hb has prooxidative and proinflammatory properties and is therefore sequestered by haptoglobin and bound by the CD163 receptor on macrophages. In the present study, we demonstrate a novel process of Hb uptake by macrophages independent of haptoglobin and CD163. Unexpectedly, macrophages do not degrade the entire Hb, but instead transfer it to neighboring cells. We have shown that the phenomenon of Hb transfer from macrophages to other cells is mainly mediated by extracellular vesicles. In contrast to the canonical Hb degradation pathway by macrophages, Hb transfer has not been reported before. In addition, we have used the process of Hb transfer in anticancer therapy, where macrophages are loaded with a Hb-anticancer drug conjugate and act as cellular drug carriers. Both mouse and human macrophages loaded with Hb-monomethyl auristatin E (MMAE) effectively killed cancer cells when co-cultured in vitro.
Authors
- Jarosław Walczak (ORCID: https://orcid.org/0000-0003-4123-763X)
- Maciej Białasek (ORCID: https://orcid.org/0000-0003-4848-342X)
- Marcin Skorzynski (ORCID: https://orcid.org/0000-0001-6665-9041)
- Tobias Weiß (ORCID: https://orcid.org/0000-0002-5533-9429)
- Michał Komorowski (ORCID: https://orcid.org/0000-0002-7293-0042)
- Aneta Magiera
- Zuzanna Sas (ORCID: https://orcid.org/0000-0001-7815-7938)
- Tomasz P. Rygiel (ORCID: https://orcid.org/0000-0003-4746-6505)
- Damian Strzemecki
- Ilona Marszałek (ORCID: https://orcid.org/0000-0002-2561-811X)
- Malgorzata Czystowska (ORCID: https://orcid.org/0000-0001-9169-6194)
- Magdalena Długołęcka (ORCID: https://orcid.org/0000-0003-2377-4693)
- Agata Braniewska (ORCID: https://orcid.org/0000-0002-2525-1290)
- Magdalena Król (ORCID: https://orcid.org/0000-0003-0421-5167)
- Marcel Bühler (ORCID: https://orcid.org/0000-0001-9608-1316)
- Łukasz Cheda (ORCID: https://orcid.org/0000-0003-3701-7917)
- Karina Kwapiszewska (ORCID: https://orcid.org/0000-0002-7396-9571)
- Daria Kurpiel
- Alberto Boffi (ORCID: https://orcid.org/0000-0003-0896-7892)
Institutions
- Warsaw University of Life Sciences (PL)
- University of Zurich (CH)
- Medical University of Warsaw (PL)
- Italian Institute of Technology (IT)
- University Hospital of Zurich (CH)
- Institute of Fundamental Technological Research (PL)
- Center for Nano Science and Technology (IT)
- Institute of Physical Chemistry (PL)
- Mossakowski Medical Research Institute, Polish Academy of Sciences (PL)
- Cell Medica (Switzerland) (CH)
- University of Warsaw (PL)
- Sapienza University of Rome (IT)
- Polish Academy of Sciences (PL)
Publication Details
- Journal
- Cell Communication and Signaling
- Published
- 2024-11-27
- DOI
- https://doi.org/10.1186/s12964-024-01929-8
- Citations
- 1
- Primary Topic
- Hemoglobin structure and function
- Type
- article
- Field-Weighted Citation Impact
- 0.33
Funders
- Fundacja na rzecz Nauki Polskiej
- Narodowe Centrum Nauki
- Universität Zürich
- Institute of Molecular and Cell Biology