Cancer stem cells characteristics: Biological function and therapeutic strategies

Tumor je heterogena nakupina tumorskih stanica, potpornih stanica te kompleksne mreže izvanstaničnog matriksa. Proces formiranja tumorske mase objašnjavaju dva modela. Prvi model odnosi se na klonalno-evolucijski model prema kojem svaka tumorska stanica ima jednak tumorogenični potencijal i svojim diobama, pod stalnim selekcijskim pritiskom tumorskog mikrookoliša, stimulira rast tumorske mase. Drugi model odnosi se na model tumorskih matičnih stanica koji predlaže kako samo određena populacija stanica ima sposobnost samoobnavljanja i proizvodnje progenitorskih stanica čime se povećava tumorska masa. Prema tome matične stanice tumora (CSC) smatraju se tumorskim-inicijatorskim stanicama, odgovornima za visoku proliferativnu moć tumora te invazivnost i metastaziranje. Metode za njihovu izolaciju i identifikaciju predstavljaju početni korak u istraživanjima njihove biologije, a danas postoji nekoliko standardiziranih metoda. Za njihovu detaljnu izolaciju i karakterizaciju često se koriste kombinirane metode koje omogućavaju precizno izoliranje CSC populacija iz početne tumorske mase. Kompleksna biologija ovih stanica oblikuje njihove fenotipske karakteristike zaslužne za svojstva pojačane invazivnosti i kemorezistencije. Među najvažnijim biološkim karakteristikama CSCs izdvajaju se načini regulacije staničnih signalnih putova odgovornih za samoobnavljanje, proliferaciju i diferencijaciju (Hedgehog, Notch i Wnt/β-katenin) te utjecaj tumorskog mikrookoliša na oblikovanje malignog fenotipa. Specijalizirana terapija koja cilja upravo CSCs, uz primjenu konvencionalne terapije, mogla bi dovesti do smanjenja ukupne mase tumora, ali i ubijanja same unutrašnje pokretačke snage tumora što bi spriječilo ponovno pojavljivanje tumora.Tumor is a heterogeneous cell population that consists of transformed tumor cells, stromal cells, and complex extracellular matrix. Tumor formation is explained by two models. First model is a clonal evolution model. This model suggests that every tumor cell has the same tumorigenic potential and that these cells, by multiple self-divisions, under the constant tumor-niche selection pressure create heterogeneous tumor. Second model is a cancer stem cell model (CSC model). This model explains tumor formation by small subpopulation of cells that can self-renew and produce cell progenies which can form heterogenous tumor. Thus, cancer stem cells (CSCs) are thought to be tumor-initiating cells responsible for tumor high proliferative power and its invasiveness. Methods for CSCs isolation and identification represent the first step in their multi-step investigation process. Today, there are few standardised methods for CSC isolation, but very often combined methods are used to precisely isolate CSCs from tumor of origin. CSCs complex biology creates phenotypic features responsible for high invasiveness and chemoresistance. Among the most responsible for those features is regulation of specialised signal-transduction pathways responsible for self-renew, proliferation and differentiation (Hedgehog, Notch i Wnt/β-catenin) and the impact of tumor-niche in creating malignant phenotype. Specialised therapy that targets CSCs, combined with conventional anticancer therapy, could lead to tumor shrinkage, tumor-core power eradication and inhibition of tumor relapse