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The Plasminogen Activation System in Human Colon Cancer: Messenger RNA for the Inhibitor PAI-1 Is Located in Endothelial Cells in the Tumor Stroma¹

Finsen Laboratory [C. P., P. K., J. E., K. D.] and Department of Pathology [E. R.], Rigshospitalet, Strandboulevarden 49, DK-2100 Copenhagen, Denmark

Fourteen human colon adenocarcinomas were examined by in situ hybridization for the presence of mRNA for plasminogen activator inhibitor type 1 (PAI-1).

All specimens contained PAI-1 mRNA in endothelial cells of some vessels in the stroma immediately surrounding the invasive tumor glands, in granulation tissue, and in some capillaries located under the free luminal surface of carcinomatous epithelium. In addition, a limited number of stromal cells in the cancerous areas located at the periphery of newly formed capillary networks, and presumably representing sprouting endothelial cells, contained PAI-1 mRNA. Cancer cells were devoid of detectable PAI-1 mRNA in all cases. PAI-1 was not seen in three biopsies of normal colon.

Together with previous findings of urokinase-type plasminogen activator and its mRNA being located in fibroblast-like cells in the tumor stroma and mRNA for the urokinase receptor in the cancer cells at invasive foci, these results indicate a complex cooperativity among several cell types in regulation of plasminogen activation in colon cancer. A possible role of PAI-1 in protecting the extracellular matrix in the tumor tissue against degradation and a role in tumor-induced angiogenesis are discussed.

¹ Supported financially by the Danish Biotechnology Programme, the Danish Cancer Society, and the Danish Medical Research Council.

² To whom requests for reprints should be addressed, at Finsen Laboratory, Rigshospitalet, Strandboulevarden 49, DK-2100 Copenhagen, Denmark.

³ Present address: Novo-Nordisk, Novo Alle, Bagsvaerd, Denmark.

Received 3/28/91. Accepted 5/ 9/91.

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