Kolorektal Kanser Metastazının Moleküler Mekanizması ve Organotropizm

Metastaz, kanser hücrelerinin anatomik olarak uzak organ bölgelerine yayılmasını ve daha sonra yabancı doku mikro ortamlarına adaptasyonunu içeren metastaz kaskadı olarak adlandırılan çok aşamalı moleküler ve biyolojik bir süreçtir. Metastaz, kolorektal kanser (KRK) hastalarında başlıca ölüm nedenidir. KRK’nin en yaygın metastaz bölgeleri karaciğer ve peritondur. Metastaz kaskadında en önemli ve geniş alanı epitelyal-mezenkimal geçiş (EMT) oluşturmaktadır. EMT, transkripsiyon faktörleri, sinyal yolakları ve miRNA’lar gibi birçok faktörün etkili olduğu bir süreçtir. Primer tümörün epitel özellikleri, integrinler ve ekzozomal integrinler, kanser kök hücre fenotipi, miRNA ekspresyonu, anjiogenez ve ekstravazasyonda etkili faktörler, organların fizyolojik özellikleri ve vaskülarizasyon metastatik yolun belirlenmesine yani organotropizme katkıda bulunmaktadır. Organotropizmde etkili olan bu mekanizmalar ayrıntılı olarak bu derlemede ele alınmaktadır. KRK’de metastaz gelişiminin altında yatan mekanizmaların daha iyi anlaşılması, metastatik KRK hastalarında hedefe yönelik tedavi açısından büyük katkı sağlayacaktır.

Molecular Mechanism of Metastasis in Colorectal Cancer and Organotropism

Metastasis is a multistep molecular and biological process called the metastasis cascade that involves the anatomically spread of cancer cells to distant organ regions and their subsequent adaptation to foreign tissue microenvironments. Metastasis is the major cause of death in colorectal cancer (CRC) patients. Liver and peritoneum are the most common metastasis sites of CRC. The epithelial-mesenchymal transition (EMT) constitutes the most important and wide area in the metastasis cascade. EMT is a process in which many factors such as transcription factors, signal pathways and miRNAs are effective. Epithelial characteristics of the primary tumor, integrins and exosomal integrins, cancer stem cell phenotype, miRNA expression, factors affecting angiogenesis and extravasation, physiological characteristics of organs and vascularization contribute to the determination of the metastatic pathway, namely organotropism. These mechanisms that are effective in organotropism are discussed in detail in this review. A better understanding of the mechanisms underlying metastasis development in CRC will greatly contribute to targeted therapy in metastatic CRC patients.

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