Block the metastases of the highway
Scientists have found out how "cancer superhighways" are formed
Polina Gershberg, Naked Science
A study published in the journal Nature Materials (Park et al., Extracellular matrix anisotropy is determined by TFAP2C-dependent regulation of cell collisions) shows how changes in tissue structure contribute to cancer cell metastasis. This work will help in the search for drugs that will prevent the spread of cancer cells throughout the body.
All tissues of the human body have a protein framework that supports their structure – the extracellular matrix. With age, this framework degrades, which leads to the appearance of signs of aging, such as wrinkles. Cancer cells can damage protein structuring elements, turning them into channels of metastasis. Scientists call such channels superhighways – this term is borrowed from the telecommunications industry and means an information network through which data is transmitted at high speed.
"These superhighways provide pathways for cancer cells to exit tumors and spread through tissues, which can have disastrous consequences for the patient," says Daniel Park, an oncology specialist and one of the authors of the work. "By understanding more about how such structures form, we can then look for ways to stop their growth and block the spread of cancer cells."
Combining the data of laboratory experiments and computer modeling, the scientists found that the shape of the protein framework depends on the interaction of fibroblasts – connective tissue cells that secrete precursor molecules of the structural proteins elastin and collagen. The interaction of these cells is regulated by the transcription factor AP-2-gamma, or TFAP2C.
Fibroblast matrices in various tissues. Drawing from the press release of The Francis Crick Institute New insights could help block the path of cancer 'super-highways' – VM.
The TFAP2C molecule indirectly controls the migration and the method of contact of fibroblasts through the expression of the RND3 protein, which is localized in the zones of intercellular collisions. RND3 is an important factor in ensuring the anisotropy of the extracellular matrix: this is a characteristic that consists in differences in the properties of the medium depending on the direction.
In the case of the extracellular matrix, the anisotropy lies in the fact that proteins accumulate unevenly in it, which serve as ligands for integrin receptors of various cells and thereby determine the direction of migration of these cells. Suppression of TFAP2C expression leads to disruption of RND3 synthesis and, as a consequence, to the formation of an isotropic matrix in which the "migration proteins" are evenly distributed. Thus, blocking TFAP2C actually prevents the formation of superhighways for the spread of cancer cells.
This work reveals new details of the mechanisms of metastasis of cancerous tumors. In addition, the data obtained during the study will help to create drugs that block the spread of metastases in the body.
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