Astrocytoma cell interaction with elastin substrates: implications for astrocytoma invasive potential.
Elastin has been identified within the meninges and the microvasculature of the normal human brain. However, the role that elastin plays in either facilitating astrocytoma cell attachment to these structures or modulating astrocytoma invasion has not been previously characterized. We have recently shown that astrocytoma cell lines and specimens produce tropoelastin, and express the 67 kDa elastin binding protein (EBP). In the present report, we have established that astrocytoma cells attach to elastin as a substrate in vitro. The U87 MG astrocytoma cell line demonstrated the greatest degree of adhesion. In addition, all astrocytoma cell lines examined were capable of penetrating and migrating through an intact elastin membrane, and of degrading tritiated-elastin, a process that could be prevented by the pre-incubation of astrocytoma cells with EDTA, but not with alpha1-antitrypsin. Astrocytoma cells were also capable of penetrating 1 mm sections of human brain tissue maintained as organotypic cultures. Interestingly, the invasive potential of cultured astrocytoma cells plated on organotypic cultures of human brain was significantly increased after exposure to elastin degradation products (kappa-elastin), which interact with astrocytoma cell surface EBP. Our data show that astrocytoma cells express a functional 67 kDa EBP, enabling them to potentially recognize and attach to elastin as a substrate. These data also suggest that this elastin receptor may be involved in processes which regulate regional astrocytoma invasion.
Jung
S
S
Sonia and Arthur Labatt Brain Tumor Research Center, Division of Neurosurgery, The Hospital for Sick Children, Toronto, Ontario, Canada.
Hinek
A
A
Tsugu
A
A
Hubbard
S L
SL
Ackerley
C
C
Becker
L E
LE
Rutka
J T
JT
D001254:Astrocytoma / Q000378:metabolism* / Q000473:pathology*; D015153:Blotting, Western; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement; D002614:Chelating Agents / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D004549:Elastin / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009924:Organ Culture Techniques; D014361:Trypsin Inhibitors / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D000515:alpha 1-Antitrypsin / Q000494:pharmacology
D002614:Chelating Agents; D014361:Trypsin Inhibitors; D000515:alpha 1-Antitrypsin; D004549:Elastin; D004492:Edetic Acid