STROMELYSIN-3 IN STROMAL TISSUE AS A CONTROL FACTOR IN BREAST-CANCER BEHAVIOR

Background. It has long been proposed that secreted proteinases, inclu ding the matrix metalloproteinases, play an important part in tumor pr ogression in mediating extracellular matrix remodeling. More recently, it has been suggested that extracellular proteinases also regulate la te growth factors and cytokines that may contribute to tumor progressi on. Methods. RNA in situ hybridization and immunohistochemistry were u sed to study the expression, in breast and other types of human carcin omas, of the stromelysin-3 (ST3) gene, which encodes a putative new me mber of the matrix metalloproteinase family. Results. The ST3 gene is overexpressed in most types of human carcinomas, including breast carc inoma where ST3 RNA was detected in 95% (99 of 104) of invasive primar y tumors. Both ST3 protein and RNA are detected in fibroblastic cells immediately surrounding the cancer cells, but not in the malignant cel ls or in stromal cells at a distance from them. The ST3 gene also is e xpressed in some in situ breast carcinomas, where ST3 expression corre lates with the known risk of these tumors to become invasive. Conclusi ons. ST3 is the paradigm of tumor proteinases that are not expressed i n the malignant cells of human carcinomas but in fibroblastic cells of tumor stroma. ST3 represents a potential new prognostic parameter to identify subpopulations of aggressive tumors, particularly to evaluate the likelihood of in situ breast carcinoma progression to invasive ca ncer. Furthermore, the specific expression of the ST3 gene in fibrobla stic cells immediately surrounding cancer cells suggests that ST3 may be involved in tumor progression and that it represents a potential ta rget for cancer treatment.