DIFFERENTIATED PRE-ADIPOCYTES ACT AS A DRIVING FORCE FOR PROSTATE CANCER PROLIFERATION, MIGRATION AND EPITHELIAL-MESENCHYMAL TRANSITION

Abstract

Obesity is a popular topic due to both its mortality and morbidity rates and related diseases such as cardiovascular diseases, diabetes and cancer. Cancer development and progression relate to many factors one of which is dysfunctional adipocytes found in the tumor microenvironment. However, underlying molecular mechanisms of the obesity-cancer link have not been fully understood. In the current study, condition media (CM) obtained from differentiated pre-adipocytes was used to set an indirect co-culture system with the prostate cancer cell line. Firstly, adipogenesis of 3T3F44-2A was checked by oil red o staining and expressions of specific genes. CM of differentiated 3T3F44-2A was applied on prostate cancer cells (PC3). Cell viability, migration capacity and related gene expression levels of the cells were evaluated. 20% CM increased cell viability after 48h. The administration also induced proliferation, migration and epithelial-mesenchymal transition (EMT)-related gene expressions. The results presented the roles of adipocytes found in the tumor microenvironment and this could allow new therapeutic developments. As a new perspective to evaluate the obesity-cancer link, our model experiment may also be useful for other cancer types. 

Keywords

• Pre-adipocyte
• Obesity
• Pre-adipocyte
• Prostate cancer cells
• Adipogenesis
• Condition media
• Tumor microenvironment
• EMT

Abstract

Obezite, hem mortalite ve morbidite oranları hem de kardiyovasküler hastalıklar, diyabet ve kanser gibi ilişkili olduğu hastalıklar nedeniyle en popüler konulardan biridir. Kanser gelişimi ve ilerlemesi, tümör mikroçevresinde bulunan işlevsiz adipositler gibi birçok faktörle ilgilidir. Bununla birlikte, obezite-kanser bağlantısının altında yatan moleküler mekanizmalar tam olarak anlaşılamamıştır. Mevcut çalışmada, farklılaştırılmış preadipositlerden elde edilen şartlandırılmış ortam (CM), prostat kanseri hücre hattı ile indirekt bir ortak kültür sistemi kurmak için kullanıldı. İlk olarak, 3T3F44-2A'nın adipogenezi, oil red o boyaması ve spesifik genlerin ifadeleri ile kontrol edildi. Farklılaştırılmış 3T3F44-2A'nın CM’si, prostat kanseri hücrelerine (PC3) uygulandı. Hücre canlılığı, migrasyon kapasitesi ve hücrelerin ilgili gen ekspresyon seviyeleri değerlendirildi. %20 CM, 48 saat sonra hücre canlılığını arttırdı. Uygulama ayrıca, proliferasyon, migrasyon ve epithelial-mesenchymal aktarım (EMT) ile ilgili gen ekspresyonlarını indükledi. Sonuçlar, tümör mikroçevresinde bulunan adipositlerin rollerini ortaya koydu ve bu, yeni terapötik gelişmelere ışık tutabilir. Obezite-kanser bağlantısını değerlendirmek için yeni bir bakış açısı olarak, model deneyimiz diğer kanser türleri için de faydalı olabilir. 

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