Modified expression of Mts1/S100A4 protein in C6 glioma cells or surrounding astrocytes affects migration of tumor cells in vitro and in vivo.
The calcium-binding Mts1/S100A4 protein plays an important role in motility and metastatic activity of tumor cells. Recently we showed that Mts1/S100A4 is expressed in white matter astrocytes and influences their migration in vitro and in vivo. Here, we have investigated the role of Mts1/S100A4 expression in C6 glioma cells or surrounding astrocytes for migration of C6 cells on astrocytes, using short interference (si) RNA to silence Mts1/S100A4 expression. We find that in vitro, the migration of Mts1/S100A4 expressing and silenced C6 cells on astrocytes is predominantly dependent on the expression of Mts1/S100A4 in astrocytes, i.e. C6 cells preferably migrate on Mts1/S100A4-silenced astrocytes. In vivo, Mts1/S100A4-positive C6 cells preferably migrate in white matter. In contrast Mts1/S100A4-silenced C6 cells avoid white matter and migrate in gray matter and meninges. Thus, the migration pattern of C6 cells is affected by their intrinsic Mts1/S100A4 expression as well as Mts1/S100A4 expression in astrocytes. To investigate if Mts1/S100A4 has a significant role on brain tumor progression, we made quantitative RT-PCR analysis for the expression of S100A4/Mts1 in various grades of astrocytic tumors. Our data showed that high-grade glioblastomas express higher amount of S100A4/Mts1 than low-grade astrocytic tumors.
Takenaga
Keizo
K
Department of Neuroscience, Biomedical Center, Box 587, Uppsala University, 751 23 Uppsala, Sweden.
Nygren
Jim
J
Zelenina
Marina
M
Ohira
Miki
M
Iuchi
Toshihiko
T
Lukanidin
Eugen
E
Sjöquist
Mats
M
Kozlova
Elena N
EN
D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001254:Astrocytoma / Q000378:metabolism / Q000473:pathology*; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D002450:Cell Communication; D045744:Cell Line, Tumor; D002465:Cell Movement; D003337:Corpus Callosum / Q000378:metabolism / Q000473:pathology; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D045726:Metalloproteases / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering; D051381:Rats; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism*
D034741:RNA, Small Interfering; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C499412:S100a4 protein, rat; C077591:S100A4 protein, human; D045726:Metalloproteases