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-kappaE). Using this system, the invasiveness of cells from four glioma cell lines was dramatically increased by the presence of kappaE and a related, specific peptide (VGVAPG)(3). In addition, MMP-2 secretion increased and MMP-12 synthesis occurred. Extracellular injections of kappaE or (VGVAPG)(3) provoked a pronounced and dose-dependent increase in [Ca(2+)](i). kappaE 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.

Uncoupling of Elastin Complex Receptor during In Vitro Aging Is Related to Modifications in Its Intrinsic Sialidase Activity and the Subsequent Lactosylceramide Production

“…EDP stimulate the proliferation of normal cells, such as fibroblasts [9,54,55] and smooth muscle cells [56], but also tumor cells from glioblastoma [57] and melanoma [15]. Consistently with literature data, our results demonstrated that EDP induce cell proliferation.…”

Essential role of microfibrillar-associated protein 4 in human cutaneous homeostasis and in its photoprotection

“…In addition to its role in the development of microfibrils, another important role of MFAP-4 in the suppression of MMP-12 activity is illustrated both in our in vivo and in vitro analyses. In parallel with previous studies indicating that elastin-derived peptides induce the expression of various kinds of MMPs (including MMP-12) in several types of cells5253 and that UV radiation alone is sufficient to selectively degrade many elastic fiber associated proteins54, the enhancement of MFAP-4 is thought to be in charge of the suppression of MMP-12 activity as well as the promotion of microfibril formation which is essential for the organization of functional elastic fibers, resulting in the observed photoprotection.…”

Heparin stimulates elastogenesis: Application to silk-based vascular grafts

“…As the threshold for elastin expression in the adult is unknown, it could be possible that the slight increase in elastin mRNA is sufficient for protein expression. Additionally, it has been reported that tropoelastin expression can cause a positive-feedback loop, which could increase levels beyond our initial mRNA findings (Coquerel et al, 2009; Wachi et al, 1995). There also may be feedback to associated elastic fibers proteins, which may regulate elastin as well.…”