Tumor Collagenase Stimulatory Factor (TCSF) Expression and Localization in Human Lung and Breast Cancers

Abstract

SUMMARYTumor cell-derived collagenase stimulatory factor (TCSF) stimulates in vitro the biosynthesis of various matrix metalloproteinases involved in tumor invasion, such as interstitial collagenase, gelatinase A, and stromelysin 1. The expression of TCSF mRNAs was studied in vivo, using in situ hybridization and Northern blotting analysis, in seven normal tissues and in 22 squamous cell carcinomas of the lung, and in seven benign proliferations and in 22 ductal carcinomas of the mammary gland. By in situ hybridization, TCSF mRNAs were detected in 40 of 44 carcinomas, in pre-invasive and invasive cancer cells of both lung and breast cancers. TCSF mRNAs and gelatinase A mRNAs were both visualized in the same areas in serial sections in breast cancers, and were expressed by different cells, tumor cells, and fibroblasts. The histological results were confirmed by Northern blot analysis, which showed a higher expression of TCSF mRNAs in cancers than in benign and normal tissues. These observations support the hypothesis that TCSF is an important factor in lung and breast tumor progression.

Expression of extracellular matrix metalloproteinase inducer and enhancement of the production of matrix metalloproteinases in rheumatoid arthritis

“…It would be difficult, however, to clearly demonstrate regulation of the expression and activity of MMPs by EMMPRIN. Previous studies have shown that EMMPRIN stimulates fibroblasts to produce 3-10 times the usual level of MMP-1 and MMP-3 in tumor cells and Chinese hamster ovary cells (20)(21)(22). The present study showed a 1.5-3 times increase in the production of MMP-1 and MMP-3.…”

Basigin (cd147) is expressed on melanoma cells and induces tumor cell invasion by stimulating production of matrix metalloproteinases by fibroblasts

“…4 CD147 is more highly expressed on the surface of most human carcinoma cells compared to their normal counterparts and correlates with tumor progression and invasion by stimulating peritumoral fibroblasts to produce elevated levels of several MMPs. 4,[11][12][13][14][15][16] These results imply that a CD147 counterreceptor might exist on the surface of fibroblasts, but none has been identified. Using CD147-transfected COS cells and immobilized recombinant CD147-Fc fusion protein, it was revealed that CD147 engages in a homophilic interaction, providing evidence that CD147 may be a counterreceptor for itself.…”

“…4,11 Expression of EMMPRIN is enhanced in a variety of human carcinomas and correlates with tumor progression and invasion by inducing production of MMPs by stromal cells. 4,[11][12][13][14][15][16] It was also shown in vitro that recombinant EMMPRIN purified from Chinese hamster ovary cells transfected with cDNA for human EMMPRIN stimulates cultured human fibroblasts to produce MMP-1, MMP-2 and MMP-3. 17 EMMPRIN not only stimulates the production of interstitial collagenase (MMP-1) but also forms a complex with MMP-1 at the human lung carcinoma cell surface, which would facilitate invasive processes.…”

New insights into the role of extracellular matrix during tumor onset and progression

“…In turn, the expression of matrix proteinases becomes regulated by tumor cells. For example, the extracellular matrix metalloproteinase inducer (EMM-PRIN) (Biswas et al, 1995) is an intrinsic plasma membrane glycoprotein produced at high levels by cancer cells (Polette et al, 1997), which stimulates adjacent stromal cells to synthesize matrix MMPs (Guo et al, 2000).…”