Recent advances in understanding the human genome have been made possible due to intensive multidisciplinary cooperation involving the life sciences and technology. Genomics has succeeded in producing complete genome DNA sequences of a number of living organisms, but we are still some way from understanding the difference between the normal and pathological functions of cells and organisms. Currently, attention is directed toward spatial and structural proteomics providing information about protein localization, structure and function, and most importantly, interactions with other proteins.
Metalloproteins are one of the most diverse classes of proteins, with intrinsic metal atoms providing a catalytic, regulatory and structural role crucial to protein functioning. One of these interesting proteins, metallothionein (MT), is known as a marker of heavy metal poisoning and could be considered a marker of tumor diseases. Despite the fact that the metal-binding abilities of MTs have been known for decades, we are the first to suggest that MTs not only protect cancer cells but also help them grow and invade the surrounding tissue, which makes a tumor more aggressive.
Exploring the role of MTs in a mechanism of tumor defense against treatment strategies based on platinum drugs is a very challenging task. There is a presumption that MT plays a crucial role in the formation of platinum-based cytostatic resistance; however, there is still no clear evidence on this phenomenon. Therefore, a multi-instrumental approach covering electrophoretic, mass spectrometric, electrochemical and immunochemical methods was utilized to test the proposed hypotheses in vitro and then in vivo. In addition, the obtained multi-instrumental data were further employed as a basis for the development and preclinical testing of biocompatible nanovehicles with smart tunable properties that could be efficient in the management of hard-to-treat tumors with frequently occurring intrinsic chemoresistance to platinum cytostatics. With this consideration in mind, the project ToMeTuM yielded a plethora of exceptional results covering novel insights into the interactions of MTs with metals, in silico tools to analyze these interactions and the construction of high-resolution 3D models of proteins that, with the advent of computational biology and chemistry, will help the community better understand the role of MTs in healthy vs. cancer cells. Furthermore, a variety of biological experiments conducted during the project revealed the importance of different isoforms of MTs for cancer aggressiveness, angiogenesis and chemoresistance to chemotherapeutics, which is of utmost importance for cutting-edge precision medicine.
