Tropoelastin and elastin degradation products promote proliferation of human astrocytoma cell lines.

Abstract

Expression of tropoelastin, the precursor of insoluble elastin and a major component of elastic fibers, has not yet been demonstrated in astrocytomas nor has it been linked to their proliferation. Here we report that human astrocytoma cell lines (U87 MG, U251 MG, U343 MG-A, U373 MG, SF 126, SF188, SF 539), as well as surgical specimens of malignant human astrocytomas, express intracellular tropoelastin. The tropoelastin produced by astrocytoma cells is, however, susceptible to proteolytic trimming to the extent that it cannot be assembled into extracellular elastic fibers. Astrocytoma cells also express the cell surface 67-kDa elastin binding protein (EBP), which binds elastin degradation products, leading to the upregulation of cyclin A and cdk2 and increased incorporation of [3H]-thymidine. The elastin-dependent mitogenic response of astrocytoma cells is abolished by lactose and chondroitin sulfate, factors which cause shedding of this 67-kDa elastin receptor from the cell surface and by blocking anti-EBP antibody. We therefore suggest that, in astrocytomas, endogenous tropoelastin degradation products bind to EBP and generate signals leading to cell cycle progression in an autocrine or paracrine manner. This is the first report implicating elastin-derived peptides as possible mitogens in malignant astrocytomas.

• Authors: S Jung, J T Rutka, A Hinek
• Journal: Journal of neuropathology and experimental neurology (J Neuropathol Exp Neurol) Vol. 57 Issue 5 Pg. 439-48 (May 1998) ISSN: 0022-3069 [Print] England
• PMID: 9596414 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclin A
• Iodine Radioisotopes
• Receptors, Cell Surface
• Tropoelastin
• elastin-binding proteins
• Elastin
• CDC2 Protein Kinase

Topics

• Astrocytoma (pathology)
• Blotting, Northern
• Brain Neoplasms (pathology)
• CDC2 Protein Kinase (metabolism)
• Cell Division (drug effects)
• Cyclin A (metabolism)
• Elastin (metabolism, pharmacology)
• Humans
• Iodine Radioisotopes
• Receptors, Cell Surface (metabolism)
• Signal Transduction (drug effects, physiology)
• Tropoelastin (metabolism, pharmacology)
• Tumor Cells, Cultured