2. Academic Validation
  3. A novel process for transcellular hemoglobin transport from macrophages to cancer cells

A novel process for transcellular hemoglobin transport from macrophages to cancer cells

  • Cell Commun Signal. 2024 Nov 27;22(1):570. doi: 10.1186/s12964-024-01929-8.
Agata Braniewska 1 2,  Marcin Skorzynski 1,  Zuzanna Sas 2 3,  Magdalena Dlugolecka 4,  Ilona Marszalek 5,  Daria Kurpiel 5,  Marcel Bühler 6,  Damian Strzemecki 5 7,  Aneta Magiera 8,  Maciej Bialasek 5 9,  Jaroslaw Walczak 10,  Lukasz Cheda 11,  Michal Komorowski 10,  Tobias Weiss 6,  Małgorzata Czystowska-Kuzmicz 12,  Karina Kwapiszewska 8,  Alberto Boffi 5 13 14,  Magdalena Krol 5 9,  Tomasz P Rygiel 15 16
Affiliations

Affiliations

  • 1 Department of Immunology, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106, Warsaw, Poland.
  • 2 Department of Immunology, Medical University of Warsaw, Warsaw, Poland.
  • 3 School of Molecular Medicine, Medical University of Warsaw, Warsaw, Poland.
  • 4 Chair and Department of Biochemistry, Doctoral School, Medical University of Warsaw, Warsaw, Poland.
  • 5 Cellis AG, Zurich, Switzerland.
  • 6 Laboratory of Molecular Neuro-Oncology, Department of Neurology, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland.
  • 7 Department of Experimental Pharmacology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland.
  • 8 Institute of Physical Chemistry, Polish Academy of Sciences, Warsaw, Poland.
  • 9 Center of Cellular Immunotherapies, Warsaw University of Life Sciences, Warsaw, Poland.
  • 10 Institute of Fundamental Technological Research, Polish Academy of Sciences, Warsaw, Poland.
  • 11 Faculty of Chemistry, University of Warsaw, Warsaw, Poland.
  • 12 Chair and Department of Biochemistry, Medical University of Warsaw, Warsaw, Poland.
  • 13 Department of Biochemical Sciences "Alessandro Rossi Fanelli", Sapienza University of Rome, Rome, Italy.
  • 14 Center of Life Nano and Neuro Science, Italian Institute of Technology, Rome, Italy.
  • 15 Department of Immunology, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106, Warsaw, Poland. trygiel@imdik.pan.pl.
  • 16 Cellis AG, Zurich, Switzerland. trygiel@imdik.pan.pl.
PMID: 39605056 DOI: 10.1186/s12964-024-01929-8
Abstract

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.

Keywords

CD163; Extracellular vesicles; Hemoglobin; Macrophages; Monomethyl auristatin E.

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