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Immunolocalization of Extracellular Matrix Proteins during Brain Tumor Invasion in BD IX Rats¹

The Rowett Research Institute, Greenburn Road, Bucksburn, Aberdeen AB2 9SB, Scotland [G. J. R., V. D., S. P. R.], and The Gade Institute, Department of Pathology, University of Bergen, N-5021 Haukeland Hospital, Bergen, Norway [O. M., R. B.]

The distribution of several native extracellular matrix proteins (type I, III, and IV collagens and fibronectin) using immunofluorescent localization is described for in two different malignant gliomas (BT4A and BT4An). In addition, antibodies against denatured forms of type I and III collagens were used to localize areas of active degradation within the tumors.

We have shown that both tumors express the native connective tissue components studied, although the distribution of these components within and between the tumors was different. In addition, native type I and III collagens and fibronectin were overexpressed in the tumors compared to the normal brain. Morphometry on immunostained type IV collagen sections showed an increase in vascular elements in both tumors compared to normal brain tissue.

The BT4A tumor, which by light microscopy showed a degradative mode of invasion, expressed denatured type I and III collagens at the tumor-brain border zone, suggesting that this tumor has collagenolytic activity.

The present article suggests that the distribution and changes in extracellular matrix protein synthesis and degradation may play an important role in the progressive growth of brain tumors in vivo.

¹ Supported by the Norwegian Cancer Society and by a FEBS fellowship.

² To whom requests for reprints should be addressed.

Received 9/13/88. Revised 4/17/89. Accepted 6/29/89.

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