Matrigel: From discovery and ECM mimicry to assays and models for cancer research

An Innovative Assay for the Analysis of In Vitro Endothelial Remodeling: Experimental and Computational Evidence

“…2 and 3). This observation is expected according to the conventional tubulogenesis assays described in literature for micro and macrovascular endothelium (Benton et al, 2014).…”

“…During this event EC move from a confluent compact monolayer (the preexisting vessel) to the ECM, that they invade and digest, and eventually organize in tubule structures. Current strategies focused on endothelial sprouting involve tridimensional spheroids of cancer cell-EC co-cultures and aortic ring assays (Benton et al, 2014). Alternative techniques allow to realistically reproduce morphologic steps and molecular events controlling human capillary tube and lumen formation in three-dimensional extracellular matrices (Davis et al, 2000;Koh et al, 2008;Vailhè et al, 2001;Saunders et al, 2006).…”

“…On the other hand, other assays that resemble the formation of tubules are regarded as representative of the later stages of angiogenesis (differentiation) and are extensively used to test novel compounds for their pro-or anti-angiogenic activity (Kleinman et al, 1986). In particular, to perform the 'endothelial tube formation assay' (or 'tubulogenesis assay'), EC are initially plated as a dispersed population in a tridimensional matrix, usually Matrigel or similar substrates, which favors cell migration and 3 differentiation in the virtual absence of cell proliferation (Benton et al, 2014). Beside its oversimplification, and the lack of a true lumen formation, this experimental protocol revealed very suitable and useful to investigate the molecular mechanisms underlying angiogenic regulation, as shown by the great amount of related publications.…”

Molecular mechanisms of neoplasia

“…The multidimensional nature of the ways to avoid apoptosis most likely reflects the number of signals it induces. nia biorą udział monocyty/makrofagi, odpowiadające za kontrolę wzajemnych oddziaływań pomiędzy komórkami utworzonych naczyń [20]. Tworzenie naczyń krwionośnych obserwuje się już w zmianach niezłośliwych, także w dysplazjach (carcinoma in situ) [21].…”

“…In neoplasms, angiogenesis is induced by proangiogenic signals that are initiated already in the early stages of tumour growth. Monocytes/macrophages participate in regulation of the vascular maturation process, and are responsible for controlling the interactions between vascular cells [20]. Angiogenesis is observed already in benign lesions, also in carcinoma in situ [21].…”