Eksozomların Kanserdeki Rolü

Abstract

Hücrelerin kanserleşmesine yol açan moleküler olaylar, mutasyonlar, DNA hasarı tamirindeki kusurlar ve hücre yaşlanması, epigenetik faktörlerle sınırlı değildir. Kanserin oluşumunda ekstrasellüler veziküllerin (EV) de rolü olduğu son yıllardaki araştırmalarla gösterilmiştir.Ekstraselüler veziküller, hücre içi ve hücreler arası sinyalizasyon, atık yönetimi ve koagülasyon gibi önemli biyolojik işlerde rol almaktadır. Hücre zarından dolaylı veya doğrudan işlemlerle oluşurlar. Ekstraselüler veziküller, hücreden oluşumu ve boyutlarına göre dört sınıfa ayrılır. Bunlar, hücre membranından doğrudan hücre dışına salınan mikroveziküller, apoptozis sonucu oluşan apoptozomlar, retrovirüs benzeri veziküller ve hücre zarından dolaylı olarak meydana gelen eksozomlardır. Eksozomlar, hücrelerden (normal ve kanser) salgılanan ve son yıllarda fonksiyonları keşfedilen hücrelerarası kargo ve haberleşme sistemleridir. Salgılandıkları hücreye özgüdürler. Nano boyutlarda oluşlarından dolayı, eksozomlar, hedef hücre tarafından kolayca tanınarak hücre içine alınır. Eksozomlar, hücre-hücre etkileşimi, sinyal iletimi, haberleşme, hücresel moleküllerin taşınması gibi birçok biyolojik olayda etkindirler. Köken aldıkları hücrelere özgü taşıdıkları moleküler belirteçler sayesinde hastalık patolojisinde de önemli rol alırlar. Bundan dolayı eksozomlar, kanser oluşumu ve yayılımında aktif fonksiyon görürler. Kanser hücrelerinden salgılanan eksozomlar, hücre membranlarıyla füzyona girerek etkilerini gösterirler. Eksozomların tümör oluşumunu tetikleyecek mikro çevre oluşturma, anjiyogenezi tetikleme, hedef hücrelerin adezyonunu, hareketliliğini ve invazyonunu değiştirerek metastaz özelliği kazandırma ve ilaç direnci geliştirme gibi katkıları olduğu ortaya çıkarılmıştır.Bu derlemede, eksozomların kanserin oluşumunda ve ilerleyişindeki rolleri ile teşhis ve tedavide kullanılabilme potansiyelinin güncel literatür ışığında değerlendirilmesi amaçlanmıştır.

Keywords

• Eksozom, immün sistem, kanser, metastaz, onkozom, vezikül.

Abstract

The molecular events that caused to produce cancerous cells are not limited to mutations, defects in DNA damage repair systems and cell senecence and epigenetic factors. Recent studies indicate that extracellular vesicles have also vital role in the formation of cancer. Extracellular vesicles are involved in important biological tasks such as intracellular and intercellular signaling, waste management and coagulation. They occur indirect or direct from cell membrane. Extracellular vesicles are divided into four classes according to their composition and size. These are microvesicles which are released directly outside from the cell membrane, apoptosomes caused by apoptosis, retrovirus-like particles and exosomes that occured indirectly from the cell membrane.In recent years exosomes that are released from all normal and cancer cells have been discovered that they function as intercellular cargo and communication systems in the human body organization. They are specific to the secreted cell. Exosomes are easily taken into the cell because of their nano size and membran structure homology with target cell. Exosomes are involved in many biological processes just as cell-cell interaction, signal transduction, communication and transport of cellular molecules. They also have an important role in the pathology of the disease because of owning specific biomarkers from the originated and secreted cells. Therefore exosomes are actively function in cancer formation and cancer progression. Exosomes secreted from cancer cells take into action by fusing its membrane with the cell’s membrane. It has been shown that exosomes contribute tumor formation and progression by inducing micro environment changes to trigger carcinogenesis and angiogenesis, by gaining metastatic ability and developing drug resistance by modifying the properties of adhesion, motility and invasion of the target cell. In this review, it was aimed to evaluate and summarize the roles of exosomes in the formation and progression of the tumor and their potential new tool in diagnosis and treatment in the light of present literature.

Keywords

• Exosome , immune system, cancer, metastasis, oncosome, vesicle.

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