Abstract 782
Background
Cell fusion (CF) is a normal biological process that plays major role in mammalian development and differentiation. Through CF, somatic cells acquire nuclear reprogramming and epigenetic modifications to form pluripotent hybrid cells, which constitute an efficient process of rapid evolution to generate hybrids with new genetic, phenotypic and functional properties at a rate exceeding that achievable by random mutagenesis. Experimental and clinical evidences indicate that CF occurs in solid tumors and contribute to cancer progression by generating progeny with metastatic features and resistance to oncologic treatments. Phosphatidylserine (PS) is a glycerophospholipid, recognized by CD36 receptor in macrophage to detect apoptotic cells. The PS-CD36 interaction is a crucial step in fusion between monocytes and tumor cells. The aim of this study is to investigate the impact of the PS-CD36 expression in macrophage–cancer cell fusion and in relation to ionizing radiation (IR).
Methods
GFP-labeled breast cancer MCF-7 cells and macrophages (differentiated monocyte cell line THP-1) were used in CF in vitro experiment with IR (figure 1). MCF-7/macrophage hybrids were generated by spontaneous CF, isolated by fluorescence activated cell sorting and confirmed by fluorescence microscopy. We treated the hybrids and their maternal cells (MCF-7 and macrophages) with IR (ɣ-irradiation, 0Gy, 2.5Gy and 5Gy). Anti-CD36 antibody, 40µg and 80µg, was used to block CD36 receptor. CF rate is based on the number of seeded macrophages, since they do not proliferate. The proportion of hybrids = (number of hybrids/number of seeded macrophages in same sample) x100.
Results
IR induces the exposure of PS (dose dependent) on MCF-7 cells, which was not found in macrophages. IR also induces significant expression of CD36 in THP-1 cells. CF was inhibited by blocking of CD36 receptor with anti-CD36 antibodies (figure 2).
Conclusions
IR induces macrophage-cancer cell fusion by stimulating the exposure of PS on MCF-7 cells and the expression of CD36 in macophages. CF and the generation of metastatic hybrids can be prevented by inhibiting the PS-CD36 interaction, a mechanism constituting an essential step in macrophage-cancer CF.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Ivan Shabo, Karolinska Institutet, Stockholm Sweden.
Funding
Swedish Society of Medicine.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
2433 - Boiling Histotripsy-induced Mechanical Ablation Modulates Tumour Microenvironment by Promoting Immunogenic Cell Death of Cancers
Presenter: Cheol-Hee Shin
Session: Poster Display session 1
Resources:
Abstract
2663 - The bacterial receptor NOD2 mediates LGR5+ intestinal stem cells protection against irradiation via mitophagy activation
Presenter: Antonin Levy
Session: Poster Display session 1
Resources:
Abstract
3213 - Pulse mode irradiation regimen of PDT results in high progression free and overall survival in mice with model tumor
Presenter: Alexey Bogdanov
Session: Poster Display session 1
Resources:
Abstract
3722 - Proton-sensitizing effect of small molecule inhibitor of P300 histone acetyltransferase C646 in human pancreatic cancer cells.
Presenter: Sungwon Shin
Session: Poster Display session 1
Resources:
Abstract
5805 - Red-Blood-Cell-Membrane-Enveloped Magnetic Nanoclusters as a Biomimetic Theranostic Nanoplatform for Bimodal Imaging Guided Cancer Photothermal Therapy
Presenter: sheng wang
Session: Poster Display session 1
Resources:
Abstract
5251 - Urine cell-free and extracellular vesicle cargo miRNAs as biomarkers for prostate cancer diagnosis
Presenter: Ivan Zaporozhchenko
Session: Poster Display session 1
Resources:
Abstract
3657 - Parkin, APEX1 and BCL2L1 Tissue Expression in Southern Brazilian Patients with Different Breast Cancer Molecular Subtypes
Presenter: Bianca Cabral
Session: Poster Display session 1
Resources:
Abstract
2839 - Obesity and prognosis in breast cancer
Presenter: Noha Ibrahim
Session: Poster Display session 1
Resources:
Abstract
5132 - SIPA1 is a modulator of HGF induced tumor metastasis via the regulation of tight junctions in lung adenocarcinoma cells
Presenter: Chang Liu
Session: Poster Display session 1
Resources:
Abstract
860 - Dose differential modulation of the autophagic behavior of estrogen expressing breast carcinoma cells
Presenter: Mariam Fouad
Session: Poster Display session 1
Resources:
Abstract