Macrophage-mediated tumorigenic effects of breast cancer cell exosomes

Yıl 2023, Cilt: 48 Sayı: 1, 289 - 296, 31.03.2023

Pervin Elvan Tokgün Samet Türel Kubilay Incı Büşra Çelikkaya Onur Tokgün

Öz

Purpose: As a heterogeneous disease, breast cancer is one of the most commonly diagnosed cancers due to hereditary/genetic factors and non-hereditary factors and is a leading cause of disease-associated death among women all over the world. Macrophages are one of the cell types that have essential roles in physiological and pathological cellular processes containing hemostasis, inflammation, and carcinogenesis. Exosomes secreted by cancer cells regulate cellular processes such as the polarization of macrophages, different organ metastasis, and drug resistance via internalized macrophages. In this study, we aimed to reveal the exosome-mediated regulation of the tumor microenvironment in specific to macrophage cells.
Materials and Methods: THP-1 monocyte cells are cultured with RPMI-1640 medium supplemented with 20 ng/ul phorbol-12-myristate-13-acetate (PMA) for 48 hours to induce macrophage differentiation. Exosomes of MCF-10A and MDA-MB-231 cells were isolated using a commercial kit. Fold changes in proliferation capacities of MCF-10A treated with exosomes of MDA-MB-231 cells were calculated.
Results: A statistically significant increase in the expression of genes involved in the inflammation-related JAK/STAT pathway in THP-1 cells treated with MDA-MB-231 exosomes was observed. Besides, we detected morphological and proliferative changes in MCF-10A cells that were co-cultured with THP-1/MDA-MB-231exo cells.
Conclusion: This study may contribute to the literature by showing that phenotypic differences in immune system cells can occur through exosomes in the tumor microenvironment.

Anahtar Kelimeler

Macrophage differentiation, exosomes, breast cancer, inflammation

Meme kanseri hücre ekzozomlarının makrofaj aracılı tümörijenik etkileri

Öz

Amaç: Kalıtsal ve genetik faktörler ile kalıtsal olmayan faktörler nedeniyle heterojen bir hastalık olan meme kanseri, tüm dünyada kadınlar arasında en sık görülen kanserlerden biridir ve hastalığa bağlı ölümlerin önde gelen nedenlerinden biridir. Makrofajlar hemostaz, inflamasyon ve karsinogenezi içeren fizyolojik ve patolojik hücresel süreçlerde önemli rollere sahip hücre tiplerinden biridir. Kanser hücreleri tarafından salgılanan eksozomlar, makrofajların polarizasyonu, farklı organ metastazı ve ilaç direnci gibi hücresel süreçleri düzenleyebilirler. Bu çalışmada makrofaj hücrelerine özgü tümör mikro çevresinin eksozom aracılı regülasyonunu ortaya koymayı amaçladık.
Gereç ve Yöntem: THP-1 monosit hücreleri, makrofaj farklılaşmasını indüklemek için 48 saat boyunca 20 ng/ul forbol-12-miristat-13-asetat (PMA) içeren RPMI-1640 besiyeri ile kültüre edildi. MCF-10A ve MDA-MB-231 hücrelerinden ticari bir kit kullanılarak eksozom izolasyonu gerçekleştirildi. MDA-MB-231 hücrelerinin eksozomları ile muamele edilen MCF-10A hücrelerinin proliferasyon kapasitelerindeki kat değişimleri değerlendirildi.
Bulgular: MDA-MB-231 eksozomları ile muamele edilen THP-1 hücrelerinde inflamasyon ile ilişkili JAK/STAT yolağında görev alan genlerin ifadesinde istatistiksel olarak anlamlı bir artış saptandı. Ayrıca THP-1/MDA-MB-231exo hücreleri ile birlikte kültüre edilen MCF-10A hücrelerinde morfolojik ve proliferatif değişiklikler saptandı.
Sonuç: Bu çalışmada tümör mikro çevresindeki eksozomlar aracılığıyla immün sistem hücrelerinde fenotipik farklılıkların oluşabileceğini göstererek literatüre katkı sağlayabilecektir.

Anahtar Kelimeler

Makrofaj farklılaşması, eksozomlar, meme kanseri, inflamasyon

Kaynakça

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