Cancer and Metastasis: Importance of Cell Adhesion Molecules and Cell Junctions

Abstract

Metastasis is a complex process which is driven by several biochemical and molecular factors. Metastasis is a condition which severely limits cancer therapies and is responsible for 90% of cancer deaths. Therefore, it is of crucial importance to gain a greater understanding of the underlying mechanisms of metastasis in terms of developing treatment methods for metastasis prevention. Included in metastasis are multiple steps such as local invasion (epithelial-mesenchymal transition), intravasation, survival in the circulatory system, extravasation (transendothelial migration/ diapedesis), formation of micrometastasis and metastatic colony. Tumor cells escape from circulating immune cells and apoptosis using platelets as a ‘‘shield’’ and a ‘‘link’’ for binding to endothelium via altering expression patterns of adhesion molecules. Extravasation in tumor cells is one of the key steps of metastasis and despite small differences in molecules, the whole process is basically the same in leukocytes; rolling, adhesion, and transmigration. Cell adhesion molecules such as integrins, and cell junctions such as Jam proteins, are key players in the extravasation step. Therefore, cell adhesion molecules and cell junctions can be used as potential targets for cancer therapy. In this review, the general processes of metastasis and the roles of cell adhesion molecules/cell junctions on metastasis were summarized.

Keywords

• metastasis,cell adhesion molecules,cell junctions

Kanser ve Metastaz: Hücre Adezyon Molekülleri ve Hücreler Arası Bağlantıların Önemi

Abstract

Kanser hücrelerinde metastaz pek çok biyokimyasal ve moleküler faktör tarafından yönlendirilen kompleks bir süreçtir. Metastaz kanser tedavilerinde yüksek oranda sınırlayıcı bir faktör olup kanserden ölümlerin %90’ından sorumludur. Bu nedenle kanser metastazında altta yatan mekanizmaların aydınlatılması kanser metastazının önlenmesi için tedavi yöntemleri geliştirmek açısından önemlidir. Metastaz, lokal invazyon (epitelyal-mezenkimal geçiş), intravazasyon, dolaşımda sağkalım, ekstravazasyon (transendotelyal migrasyon/diapedez), mikrometastaz oluşumu ve metastatik koloni oluşumu gibi basamakları içermektedir. Tümör hücreleri integrin selektin gibi adezyon moleküllerinde yaptıkları ekspresyon değişimleri aracılığıyla plateletleri ‘‘kalkan’’ ve endotele bağlanmak için ‘‘aracı’’ olarak kullanarak dolaşımdaki immün sistem hücrelerinden ve apoptoztan kaçarlar. Tümör hücrelerinde ekstravazasyon metastazın anahtar basamaklardan biridir ve moleküllerde ufak farklılıklar olsa da tüm süreç temel olarak lökositlerde olduğu gibidir; yuvarlanma, adezyon ve transmigrasyon (diapedez). İntegrinler gibi hücre adezyon molekülleri ve Jam proteinleri gibi hücreler arası bağlantılar ekstravazasyon aşamasında kilit rollere sahiptir. Bu sebeple hücre adezyon molekülleri ve hücreler arası bağlantılar kanser tedavisinde potansiyel hedefler olarak kullanılabilir. Bu derlemede kanser metastazında yer alan genel süreçler ile hücre adezyon molekülleri ve hücreler arası bağlantıların metastazdaki rolleri özetlenmiştir.

Keywords

• Kanser,metastaz,adezyon molekülleri,hücreler arası bağlantılar

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