Tumorigenic Potential of Extracellular Matrix Metalloproteinase Inducer
| Autor: | Hussein D. Foda, Jian Cao, Michelle Hymowitz, David C. Tompkins, Bryan P. Toole, Stanley Zucker, Cathleen E. Conner, Richard Mann, Ellen E. Rollo |
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| Rok vydání: | 2001 |
| Předmět: |
Pathology
medicine.medical_specialty Stromal cell Short Communication Green Fluorescent Proteins Gelatinase A Mice Nude Matrix metalloproteinase Biology Transfection medicine.disease_cause Pathology and Forensic Medicine Mice Antigens CD Antigens Neoplasm Tumor Cells Cultured medicine Animals Humans Collagenases RNA Messenger Fibroblast In Situ Hybridization Membrane Glycoproteins Histocytochemistry Mammary Neoplasms Experimental Cancer medicine.disease Luminescent Proteins medicine.anatomical_structure Basigin Cancer cell Cancer research Female Indicators and Reagents Carcinogenesis Cell Division |
| Zdroj: | The American Journal of Pathology. 158:1921-1928 |
| ISSN: | 0002-9440 |
| Popis: | Extracellular matrix metalloproteinase inducer (EMMPRIN), a glycoprotein present on the cancer cell plasma membrane, enhances fibroblast synthesis of matrix metalloproteinases (MMPs). The demonstration that peritumoral fibroblasts synthesize most of the MMPs in human tumors rather than the cancer cells themselves has ignited interest in the role of EMMPRIN in tumor dissemination. In this report we have demonstrated a role for EMMPRIN in cancer progression. Human MDA-MB-436 breast cancer cells, which are tumorigenic but slow growing in vivo, were transfected with EMMPRIN cDNA and injected orthotopically into mammary tissue of female NCr nu/nu mice. Green fluorescent protein was used to visualize metastases. In three experiments, breast cancer cell clones transfected with EMMPRIN cDNA were considerably more tumorigenic and invasive than plasmid-transfected cancer cells. Increased gelatinase A and gelatinase B expression (demonstrated by in situ hybridization and gelatin substrate zymography) was demonstrated in EMMPRIN-enhanced tumors. In contrast to de novo breast cancers in humans, human tumors transplanted into mice elicited minimal stromal or inflammatory cell reactions. Based on these experimental studies and our previous demonstration that EMMPRIN is prominently displayed in human cancer tissue, we propose that EMMPRIN plays an important role in cancer progression by increasing synthesis of MMPs. |
| Databáze: | OpenAIRE |
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