Modeling the epithelial-mesenchymal transition process in a 3D organotypic cervical neoplasia

Organ on Chip Technology to Model Cancer Growth and Metastasis

“…However, recent works [ 40 ] demonstrated that exogenous hydrogel such as Collagen, fibrin, Matrigel, while effective in vitro matrices for cells cultures, often fail in recapitulating the diverse biochemical and physical aspects of native tumoral ECM. In this perspective, recently decellularized ECM [ 59 , 60 ], and cell synthesized matrices [ 12 , 56 , 61 , 62 ] have been used as 3D matrices for cell culture in order to increase the complexity and increase the pato-physiological relevance of the TME in vitro. Along this line, Hughes et al extracted and compared ECM from normal human colon tissue and colon tumor metastases and found differences in protein composition and stiffness between the two reconstituted matrices with overrepresentation of several matrix proteins in the tumor ECM as well as an increase in stiffness compared to normal ECM.…”

“…A variety of tumor types, including those developing in the skin, bladder, and eye tissues have been developed with this approach [ 56 ]. On the other side, bioengineering approaches based on the use of engineered microtissues have been developed in our group, both by using single tumoral microtissue as in vitro cancer model [ 12 , 13 ], or by using engineered microtissues as building block in a modular tissue engineering approach [ 61 ]. The latter also takes advantage of endogenous cell-specific self-synthesized ECM and assembly, promoted by culture conditions in bioreactor, cell-materials interaction and ascorbate [ 65 ].…”

“…The latter also takes advantage of endogenous cell-specific self-synthesized ECM and assembly, promoted by culture conditions in bioreactor, cell-materials interaction and ascorbate [ 65 ]. Recently, by following this approach we succeeded in developing an organotypic cervical cancer models by seeding organ-specific cancer epithelial cells on endogenous ECM synthesized, assembled and populated by normal or cancer-associated fibroblasts to investigate the role of diseased stromal environment in guiding the epithelial-mesenchymal transition process [ 61 ]. Taken together, these observations highlight the relevance of studying tumor cells in the correct physico-chemical context.…”

RNA Sequencing and Cell Models of Virus-Associated Cancer (Review)

“…It is believed that a single spheroid roughly corresponds to a tumor microdomain (a microregion of tumor tissue enclosed between the branches of the capillary network), reviews so this model better reproduces physicochemical gradients and differences in proliferation/apoptosis/ necrosis rates within a single microsite. As the authors of systematized reviews note [45][46][47], the use of spheroid cultures and other 3D models in HNC/CC studies is in the initial stage of development (mainly in the stage of optimizing experimental protocols), while the area of cell spheroid application is limited mainly to routine types of analysis in which the ability of cells to spheroidogenesis is considered only as an indicator of the degree of expression of the somatic stem cell traits. If we turn to works that use a spheroid culture precisely as a model for recreating a certain cell state, which is then analyzed using RNA-Seq, then we can see that spheroids for cervical cancer (cervospheres) were derived from standard tumor lines (HeLa, SiHa, CaSki), but not from patient-derived primary cells.…”

“…An organotypic raft culture can be generated not only for stratified normal or dysplastically altered epithelium but also for early, intraepithelial cancer; in this case, it can serve as a model of early invasion. This possibility was demonstrated in two works on cervical cancer [75] and [46], while the study by De Gregorio et al [46] paid particular attention to generating a 3D stroma model, consisting of primary tumor-associated cervical reviews fibroblasts and the extracellular matrix also produced by them. The authors point out that the connective tissue base in such a culture is not just a substrate, but an equal participant in crosstalk between tumor and stromal cells, and it is the authentic stroma that properly reproduces the signals of the microenvironment necessary for cervical cancer cells to undergo EMT and activate invasion.…”