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Tissue inhibitor of metalloproteinases-1 (TIMP-1) RNA is expressed at
elevated levels in malignant non-Hodgkin's lymphomas
AE Kossakowska, SJ Urbanski and DR Edwards
Department of Pathology, University of Calgary, Alberta, Canada.
Secreted metalloproteinases (MPs) and their specific inhibitors (TIMPs,
tissue inhibitors of MPs) are important mediators of extracellular matrix
metabolism. Previous studies have linked either excessive MP release or
reduced TIMP-1 production to the invasive and metastatic phenotypes of
cancer cells. In the present study we investigated the relationship between
the expression of TIMP-1 and the clinical behavior of 28 non-Hodgkin's
lymphomas. Northern blot analysis showed that levels of TIMP-1 mRNAs
correlated directly with clinical aggressiveness: tumors in the high-grade
category contained the highest levels of TIMP-1 transcripts approaching
those found in maximally growth factor-stimulated fibroblasts in vitro. In
situ hybridization localized the TIMP-1 expression to stromal cells of
endothelial and fibroblastic origin. In contrast, transcripts hybridizing
with metalloproteinase gene probes (interstitial collagenase and 72-Kd type
IV collagenase) were expressed at very low levels in malignant lymphomas
and their expression was not coordinately regulated with that of TIMP-1.
The majority of tumors expressed either interstitial collagenase or 72-Kd
type IV collagenase, and only a small number expressed both. Interstitial
collagenase transcripts were only detected in high-grade tumors. The
relative levels of TIMP-1 expression did not correlate with the degree of
fibrosis of the tumors. Our data suggest the importance of tumor-stromal
interactions in non-Hodgkin's lymphomas, and moreover, our results indicate
a possible relationship between high-level, localized expression of TIMP-1
and the malignant phenotype of high-grade advanced-stage lymphomas.
Volume 77,
Issue 11,
pp. 2475-2481,
06/01/1991
Copyright © 1991 by The American Society of Hematology
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