BACKGROUND: Tumour cells utilize different migration strategies to invade surrounding tissues and elude anticancer treatments. It is therefore important to understand the mechanisms underlying migration process, in order to aid the development of therapies aimed at blocking the dissemination of cancer cells. AIMS: In this study tumour cell lines of different histological origin were analysed by combining 2D and 3D in vitro assays, biochemical tests and high resolution imaging by scanning electron microscopy (SEM) in order to look insight strategies adopted by tumour cells to invade extracellular matrix. RESULTS: Quantitative (computer-assisted colour camera equipped-light microscopy) and qualitative analysis (SEM) indicated that the most aggressive tumour cells adopt an "individual" behaviour. The analysis of intracellular signalling demonstrated that the highest invasive potential was associated with the activation of AKT, ERK, FAK and ERM proteins. The "individual" behaviour was positively related to the expression of VLA-2 and inversely related with the E-cadherin expression. CONCLUSIONS: The combination of 2D and 3D in vitro assays, biochemical tests and ultrastructural investigations proved to be a suitable test for the investigation of tumour cell migration and invasion. The high resolution imaging by SEM highlighted the interrelationships between cells in different migratory behaviours of tumour cells.
Background. Issues regarding cancer stem cell (CSC) movement are important in neurosphere biology as cell-cell or cell-environment interactions may have significant impacts on CSC differentiation and contribute to the heterogeneity of the neurosphere. Aims. Despite the growing body of literature data on the biology of brain tumor stem cells, floating CSC-derived neurospheres have been scarcely characterized from a morphological and ultrastructural point of view. Results. Here we report a morphological and ultrastructural characterization performed by live imaging and scanning electron microscopy. Glioblastoma multiforme (GBM) CSC-derived neurospheres are heterogeneous and are constituted by cells, morphologically different, capable of forming highly dynamic structures. These dynamic structures are regulated by not serendipitous cell-cell interactions, and they synchronously pulsate following a cyclic course made of "fast" and "slow" alternate phases. Autocrine/paracrine non canonical Wnt signalling appears to be correlated with the association status of neurospheres. Conclusions. The results obtained suggest that GBM CSCs can behave both as independents cells and as "social" cells, highly interactive with other members of its species, giving rise to a sort of "multicellular organism".
Cell migration and invasion are crucial steps in many physiological events. However, they are also implicated in the physiopathology of many diseases, such as cancer. To spread through the tissues, tumor cells use mechanisms that involve several molecular actors: adhesion receptor families, receptor tyrosine kinases, cytoskeleton proteins, adapter and signalling proteins interplay in a complex scenario. The balance of cellular signals for proliferation and survival responses also regulates migratory behaviours of tumor cells. To complicate the scene of crime drug resistance players can interfere thus worsening this delicate situation. The complete understanding of this molecular jungle is an impossible mission: some molecular aspects are reviewed in this paper.
La migrazione e l'invasione cellulare rappresentano momenti cruciali in molti eventi fisiologici: questi due processi, tuttavia, sono anche implicati nella fisiopatologia di varie malattie, tra cui i tumori. Per diffondersi attraverso i tessuti, le cellule tumorali ricorrono a meccanismi che vedono il coinvolgimento di diversi componenti cellulari: famiglie di molecole di adesione, recettori tirosinchinasi, proteine del citoscheletro, proteine di segnalazione intracellulare intervengono in un complesso scenario molecolare. Le vie di segnalazione regolanti i processi di sopravvivenza e proliferazione cellulare giocano un ruolo importante anche nei comportamenti migratori delle cellule tumorali. A complicare la scena del crimine, marcatori proteici della farmacoresistenza contribuiscono al conferimento di un fenotipo maggiormente aggressivo, peggiorando in tal modo una situazione già di per sé delicata. La comprensione completa di questa "giungla molecolare" è una missione impossibile: in questa rassegna verranno presi in considerazione alcuni degli aspetti molecolari.