Dual role of tumor associated macrophages in acquired resistance to second-generation androgen receptor antagonists in hormone sensitive prostate cancer cells

Creative Commons License

Hunç F., Duruksu G., Yazır Y., Dillioğlugil M. Ö.

49th FEBS Congress: Bridging Continents to Advance Life Science, İstanbul, Türkiye, 5 - 09 Temmuz 2025, cilt.15, ss.26-27, (Özet Bildiri)

  • Yayın Türü: Bildiri / Özet Bildiri
  • Cilt numarası: 15
  • Doi Numarası: 10.1002/2211-5463.70069
  • Basıldığı Şehir: İstanbul
  • Basıldığı Ülke: Türkiye
  • Sayfa Sayıları: ss.26-27
  • Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
  • Kocaeli Üniversitesi Adresli: Evet

Özet

Dual role of tumor associated macrophages in acquired resistance to second-generation androgen receptor antagonists in hormone sensitive prostate cancer cells

HUNC, Fatih1; DURUKSU, Gökhan2; YAZIR, Yusufhan2; DILLIOGLUGIL, Meltem1;


1Department of Biochemistry, School of Medicine, Kocaeli University, Türkiye

2Kocaeli University Center for Stem Cell and Gene Therapies Research and Practise, Türkiye

Second-generation androgen reseptor antagonists, have provided remarkable advancements in prostate cancer (PCa) patients, unless acquired resistance to antiandrogen treatment, which can be altered by inflammatory tumor microenvironment (TM), restricts therapy success. Functionally distinct subtypes of tumor associated macrophages (TAMs): pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages, are major modulators for the formation of TM.  In this research, we aimed to assess their impact on therapy response and determinants for the acquired antiandrogen resistance.

Elucidation of M1 and M2 TAMs driven effects on the theurapeutic efficacy of a novel antiandrogen apalutamide was performed using with LNCaP cell line. Conditioned medium (CM) was used to create in vitro inflammatory TM.

According to the flow cytometric analysis of annexin V-stained LNCaP cells, M2 polarized TAMs mediated cellular responses of cancer cells abolished apalutamide induced total apoptosis, compared to the M1 polarized TAMs. Besides, cell viability was found to be preserved in similar pattern. Additionally, intracellular ROS levels were found to be lower in PCa group, treated with CM obtained from M2 polarized TAMs compared to the M1 polarized TAMs.

M1 macrophages, typically associated with anti-tumor activity, may paradoxically induce chronic inflammation, fostering genetic instability and therapy resistance. Conversely, M2 macrophages, known for their pro-tumorigenic properties, promote immunosuppression, angiogenesis, and epithelial-to-mesenchymal transition (EMT), thereby facilitating resistance to antiandrogens. These findings indicate the substantial role of different polarization of TAMs in acquired resistance to antiandrogens, and provide insights for the development of potential new therapeutic approaches in PCa.

This project is supported by TUBITAK 1002 Program (Project No: 122S828).