Source : Elastin‐derived peptides: Matrikines critical for glioblastoma cell aggressiveness in a 3‐D system

Abstract

In the most common primary brain tumors, malignant glioma cells invade the extracellular matrix (ECM) and proliferate rapidly in the cerebral tissue, which is mainly composed of hyaluronan (HA) along with the elastin present in the basement membrane of blood vessels. To determine the role of ECM components in the invasive capacity of glioma cell lines, we developed a 3‐D cell‐culture system, based on a hydrogel in which HA can be coreticulated with kappa‐elastin (HA‐κE). Using this system, the invasiveness of cells from four glioma cell lines was dramatically increased by the presence of κE and a related, specific peptide (VGVAPG)3. In addition, MMP‐2 secretion increased and MMP‐12 synthesis occurred. Extracellular injections of κE or (VGVAPG)3 provoked a pronounced and dose‐dependent increase in [Ca2+]i. κE significantly enhanced the expression of the genes encoding elastin‐receptor and tropoelastin. We propose the existence of a positive feedback loop in which degradation of elastin generates fragments that stimulate synthesis of tropoelastin followed by further degradation as well as migration and proliferation of the very cells responsible for degradation. All steps in this ECM‐based loop could be blocked by the addition of either of the EBP antagonists, lactose, and V‐14 peptide, suggesting that the loop itself should be considered as a new therapeutic target.


gregory

gregory

Grégory MAUBON is Chief Data Officer and digital coordinator at HCS Pharma, a biotech startup focused in high content screening and complex diseases. He manages IT missions and leads digital usages linked to company needs. He is also a Augmented Reality Evangelist (presenter and lecturer) since 2008, where he created www.augmented-reality.fr and founded in 2010 RA'pro (the augmented reality promotion association). He helped many companies (in several domains) to define precisely their augmented reality needs and supported them in the implementation.

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