engleski

Differences in anticancer drug sensitivities in 3D and 2D cancer cell culture systems: model on ADAM10 novel anticancer drug target and biomarker

Overexpression and activation of HER-2 protein has implication in the development and progression of a variety of tumor types. ADAM10, a transmembrane protein implicated in proteolytic extracellular domain (ECD) release of the HER-2 receptor tyrosine kinase, is an important regulator of cell proliferation and survival in 25% of breast cancers. Cleavage of HER-2 ECD in HER-2 overexpressing human breast cancer cell lines like SK-BR-3, results in a constitutively activated truncated membrane bound kinase and thus in ligand independent signalling. High levels of circulating ECD of HER2 are correlated with poor patient prognosis since ECD contains the binding area for monoclonal antibody (Herceptin). Combination of monoclonal antibody that targets HER-2 in subsaturating concentration and ADAM10 inhibitors that targets photolytic activity, results in decreased proliferation of HER2 overexpressing cell lines (1). The usual standards for testing the influence of new chemical entities (NCE) on cellular functions and physiological responses present in organs are 2D cell culture testing platforms. However, a significant number of such functions are lost with conventional 2D approach, which give arise to a more frequent use of 3D cell culture systems, crucial for cellular behavior and tumorogenicity (2, 3). 3D approach overcome difference in cell morphology, proliferation and differentiation that enable more precise biological insights into cellular functions.

ADAM-10; cancer biomarkers; drug sensitivities 3D vs 2D cell cultures

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