Metastaz ve Hücresel Göç Mekanizmaları
Özet
Metastaz, kanser progresyonunun en kritik ve mortal evresini oluşturmakta olup, kansere bağlı ölümlerin büyük bir kısmından sorumludur. Primer tümörler sıklıkla lokal tedavilerle kontrol altına alınabilse de, metastatik hastalık sistemik yayılım göstermesi nedeniyle tedavisi güç bir tablo ortaya koymaktadır. Metastaz; tümör hücrelerinin primer odaktan ayrılması, invazyon, intravazasyon, dolaşımda hayatta kalma, ekstravazasyon ve uzak dokularda kolonizasyon gibi çok aşamalı ve karmaşık biyolojik süreçleri içermektedir. Bu süreçlerde epitelyal-mezenkimal geçiş (EMT), hücresel göç mekanizmaları, adezyon molekülleri, proteazlar ve çeşitli sinyal yolakları merkezi roller üstlenmektedir. Ayrıca tümör mikroçevresi, stromal ve immün hücrelerle kurulan etkileşimler ile premetastatik nişlerin oluşumu, metastatik hücrelerin hayatta kalmasını ve kolonizasyon yeteneğini önemli ölçüde etkilemektedir. Dolaşımdaki tümör hücreleri (CTC’ler) ve özellikle CTC kümeleri, metastatik başarı açısından kritik öneme sahiptir. Bu derlemede metastazın hücresel ve moleküler temelleri, hücre göç mekanizmaları ve metastatik kolonizasyon süreci güncel literatür ışığında ele alınmıştır. Metastazın karmaşık biyolojisinin daha iyi anlaşılması, gelecekte metastaza özgü tanı ve tedavi stratejilerinin geliştirilmesine katkı sağlayacaktır.
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