An Overview of Association Between Exosomes and Lung Cancer

Yıl 2020, , 114 - 120, 01.01.2020

Emine Yağcı , Cansu Ozbayer , Hülyam Kurt

https://doi.org/10.20515/otd.517996

Öz

Exosomes; are bioactive receptors which is indirectly
originating from the cell membrane. The dimensions vary between 50-140 nm. The
most important features distinguishing exosomes from other extracellular
vesicles (microvesicles and apoptotic bodies) are their unique biogenesis
pathways, lipid compositions, and RNA cargos (mRNA, miRNA, lncRNA) they carry.
Exosomes that play a role in cell-cell interaction by virtue of their RNA
content can alter the transcriptome and function of the cell with the RNA
strands they carry when transferred to the recipient cell. It has also been
identified that they carry nucleic acids (DNA, RNA), proteins, nucleoproteins
and various enzymes for use in signal transduction. Exosomes are also secreted
by cancer cells and tumor-associated stromal cells as they are secreted from
healthy cells under physiological conditions. Through the exosomes, autocrine,
paracrine and endocrine communication is established between cancer cells.
Although exosomal secretion is a normal process, the increase in rate and
exosomal mediated transfer of different cargos (oncogenic signals) may mediate
oncogenic progression and metastasis. The increase in exosomal quantities and
altered cargo expression can be considered as a powerful biomarker for altering
normal physiological conditions and can be used to diagnose cancer and many
other diseases. Exosomes can be obtained by ultracentrifugation from body
fluids such as blood, plasma, cerebrospinal fluid, bile, breast milk, amniotic
fluid, saliva, urine and can be evaluated for molecular components such as DNA,
RNA, miRNA, and proteins. In addition, as they are derived from the plasma
membrane, they are inherently liposomal and nano-sized and can easily move
through the blood-brain barrier, due to their protein-lipid content in their
membranes. Although exosomes are associated with many types of cancer, they are
also important in lung cancer. It has been showed that exosomes are increasing
lung endothelial permeability and lung metastasis, and also plays an important
role in angiogenesis in lung cancer. As a result, exosomes are smart munchkins
carrying cargo between cells and have the ability to convert healthy cells to
carcinoma according to the cargo that they carry. They can also be obtained
from whole-body fluids and can be used for targeted treatment with their
ability to enter the cells easily and to carry them in circulation. 

Eksozomlar ve Akciğer Kanseri Arasındaki İlişkiye Genel Bakış

Öz

Eksozomlar; hücre
zarından indirekt olarak köken alan biyoaktif reseptörlerdir. Boyutlar 50-140
nm arasında değişmektedir. Eksozomları diğer hücre dışı veziküllerden
(mikro-veziküller ve apoptotik cisimler) ayırt eden en önemli özellikler,
kendilerine özgü biyolojik oluşum yolakları, lipit bileşimleri ve taşıdıkları
RNA yükleridir (mRNA, miRNA, lncRNA). RNA içerikleri sayesinde hücre-hücre
etkileşmesinde rol oynayan ekzomlar, alıcı hücreye aktarıldıklarında
taşıdıkları RNA iplikleriyle hücrenin transkriptomunu ve işlevini
değiştirebilir. Ayrıca, sinyal iletiminde kullanım için nükleik asitleri (DNA,
RNA), proteinleri, nükleoproteinleri ve çeşitli enzimleri taşıdıkları
bilinmektedir. Eksozomlar fizyolojik koşullar altında sağlıklı hücrelerden
salgılanmakla birlikte kanser hücreleri ve tümörle ilişkili stromal hücreler
tarafından da salgılanır. Eksozomlar sayesinde kanser hücreleri arasında otokrin,
parakrin ve endokrin iletişim kurulur. Eksozomal salınım normal bir süreç olsa
da, farklı kargoların (onkojenik sinyaller) hız ve ekzomal aracılı
transferindeki artış onkojenik ilerlemeye ve metastaza neden olabilir. Eksozom
miktarlardaki artış ve kargo ifadesinin değişmesi normal fizyolojik koşulları
değiştirmek için güçlü bir biyobelirteç olarak kabul edilebilir ve kanseri ve
diğer birçok hastalığı teşhis etmek için kullanılabilir. Eksozomlar, kan,
plazma, beyin omurilik sıvısı, safra, anne sütü, amniyon sıvısı, tükürük, idrar
gibi vücut sıvılarından ultrasantrifüj yoluyla elde edilebilir ve DNA, RNA,
miRNA ve proteinler gibi moleküler bileşenler için değerlendirilebilir. Ek
olarak, bunlar plazma zarından köken aldığı için, doğal olarak lipozomal ve
nano boyuttadırlar ve böylelikle zarlarındaki protein-lipid içeriğinden dolayı
kan beyin bariyeri boyunca kolayca hareket edebilirler. Eksozomlar birçok
kanser türüyle ilişkilendirilse de, akciğer kanserinde de önemlidir.
Eksozomların akciğerdeendotel geçirgenliğini ve akciğer metastazını arttırdığı
ve ayrıca akciğer kanserinde anjiyogenezde önemli bir rol oynadığı
gösterilmiştir. Sonuç olarak, eksozomlar hücreler arasında kargo taşıyan akıllı
moleküllerdir ve taşıdıkları yüke göre sağlıklı hücreleri karser hücresine
dönüştürme kabiliyetine sahiptir. Ayrıca tüm vücut sıvılarından da elde
edilebilirler ve hücrelere kolayca girme ve dolaşımda taşıma yetenekleriyle
hedeflenen tedavi için kullanılabilirler.

Anahtar Kelimeler

Exosome, kanser, metastaz, anjiogenez

Kaynakça

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