Autotaxin: a secreted autocrine/paracrine factor that promotes glioma invasion.
Glioblastoma multiforme (GBM) is inherently invasive, and it is from the invasive cell population that the tumor recurs. The GBM invasion transcriptome reveals over-expression of various autocrine factors that could act as motility drivers, such as autotaxin (ATX). Some of these factors could also have paracrine roles, modulating the behavior of cells in the peri-tumoral brain parenchyma. ATX generates lysophosphatidic acid (LPA), which signals through LPA receptors expressed by GBM as well as in astrocytes, oligodendrocytes (ODC) and microglia; their activation manifest cell specific effects. ATX stimulates invasion of GBM cells in vitro and ex vivo invasion assays. ATX activity enhances GBM adhesion in cells expressing the LPA1 receptor, as well as stimulating rac activation. GBM secreted ATX can also have paracrine effects: ATX activity results in reduced ODC adhesion. ODC monolayer invasion showed that U87 and U251 GBM cells expressing ATX invaded through an ODC monolayer significantly more than cells depleted of ATX or cells expressing inactive ATX, suggesting that GBM cells secreting ATX find ODCs less of a barrier than cells that do not express ATX. Secreted factors that drive GBM invasion can have autocrine and paracrine roles; one stimulates GBM motility and the other results in ODC dis-adhesion.
Hoelzinger
Dominique B
DB
Cancer and Cell Biology Division, Translational Genomics Research Institute, 445 North 5th Street, 5th floor, Phoenix, AZ 85004, USA.
Nakada
Mitsutoshi
M
Demuth
Tim
T
Rosensteel
Tyler
T
Reavie
Linsey B
LB
Berens
Michael E
ME
D000818:Animals; D001921:Brain / Q000503:physiopathology; D001932:Brain Neoplasms / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology*; D005909:Glioblastoma / Q000378:metabolism*; D005956:Glucose-6-Phosphate Isomerase / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D043264:Phosphodiesterase I / Q000235:genetics / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D013997:Time Factors; D019737:Transplants; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D000099189:Lysophospholipase D
D005956:Glucose-6-Phosphate Isomerase; D008070:Lipopolysaccharides; D009097:Multienzyme Complexes; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; D034741:RNA, Small Interfering; D020830:rac1 GTP-Binding Protein; D000099189:Lysophospholipase D