Cellular accumulation of uPA-PAI-1 [correction of UPA-PAI-1] and uPA-PAI-2 [correction of UPA-PAI-2] complexes in early (pT1) breast cancer: a new link in the uPA-UPAr-PAI chain. 2000

J Schneider, and R Lucas, and J Sánchez, and A Tejerina, and A Ruibal
Fundación Tejerina-Centro de Patología de la Mama, Madrid, Spain. schneider@teleline.es

OBJECTIVE To investigate the role of uPA in early (pT1) breast cancer. METHODS Immunohistochemistry (streptavidin-biotin-peroxidase system), using the Chemicon AB776 polyclonal antibody, which reacts with uPA-PA-1 and uPA-PAI-2 complexes, was performed. In addition, CD44std, Ki67, c-erb-B2, p53, ER and PR expression were studied on the same tissue samples by the same method. The results obtained were correlated with nodal invasion, with each other and with classical pathologic features such as histologic and nuclear grade by means of the Spearman test for nonparametric variables. RESULTS The immunohistochemical reaction with uPA-PAI-1 and uPA-PAI-2 complexes was cytoplasmic and localized inside the tumor cells, with no, or only minimal reaction in the stromal cells. uPA-positivity detected by this method correlated significantly with ER expression (p = 0.031), PR expression (p = 0.030), favorable nuclear grade (p = 0.0087) and marginally with a low proliferation rate (p = 0.088), which was the opposite of the results reported by most other groups when studying either free uPA or uPA bound to its membrane receptor (uPAr) in similar tumors. CONCLUSIONS From our results we conclude that uPA-PAI-1 and uPA-PAI-2 complexes are formed inside the tumor cells for the purpose of inactivating free or uPAr-bound uPA, which explains why our findings were the reverse of those obtained when studying these latter forms. A model incorporating our data and the present knowledge on the uPA-uPAr-PAI chain is proposed.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008207 Lymphatic Metastasis Transfer of a neoplasm from its primary site to lymph nodes or to distant parts of the body by way of the lymphatic system. Lymph Node Metastasis,Lymph Node Metastases,Lymphatic Metastases,Metastasis, Lymph Node
D009361 Neoplasm Invasiveness Ability of neoplasms to infiltrate and actively destroy surrounding tissue. Invasiveness, Neoplasm,Neoplasm Invasion,Invasion, Neoplasm
D011960 Receptors, Estrogen Cytoplasmic proteins that bind estrogens and migrate to the nucleus where they regulate DNA transcription. Evaluation of the state of estrogen receptors in breast cancer patients has become clinically important. Estrogen Receptor,Estrogen Receptors,Estrogen Nuclear Receptor,Estrogen Receptor Type I,Estrogen Receptor Type II,Estrogen Receptors Type I,Estrogen Receptors Type II,Receptor, Estrogen Nuclear,Receptors, Estrogen, Type I,Receptors, Estrogen, Type II,Nuclear Receptor, Estrogen,Receptor, Estrogen
D011980 Receptors, Progesterone Specific proteins found in or on cells of progesterone target tissues that specifically combine with progesterone. The cytosol progesterone-receptor complex then associates with the nucleic acids to initiate protein synthesis. There are two kinds of progesterone receptors, A and B. Both are induced by estrogen and have short half-lives. Progesterone Receptors,Progestin Receptor,Progestin Receptors,Receptor, Progesterone,Receptors, Progestin,Progesterone Receptor,Receptor, Progestin
D001943 Breast Neoplasms Tumors or cancer of the human BREAST. Breast Cancer,Breast Tumors,Cancer of Breast,Breast Carcinoma,Cancer of the Breast,Human Mammary Carcinoma,Malignant Neoplasm of Breast,Malignant Tumor of Breast,Mammary Cancer,Mammary Carcinoma, Human,Mammary Neoplasm, Human,Mammary Neoplasms, Human,Neoplasms, Breast,Tumors, Breast,Breast Carcinomas,Breast Malignant Neoplasm,Breast Malignant Neoplasms,Breast Malignant Tumor,Breast Malignant Tumors,Breast Neoplasm,Breast Tumor,Cancer, Breast,Cancer, Mammary,Cancers, Mammary,Carcinoma, Breast,Carcinoma, Human Mammary,Carcinomas, Breast,Carcinomas, Human Mammary,Human Mammary Carcinomas,Human Mammary Neoplasm,Human Mammary Neoplasms,Mammary Cancers,Mammary Carcinomas, Human,Neoplasm, Breast,Neoplasm, Human Mammary,Neoplasms, Human Mammary,Tumor, Breast
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014568 Urokinase-Type Plasminogen Activator A proteolytic enzyme that converts PLASMINOGEN to FIBRINOLYSIN where the preferential cleavage is between ARGININE and VALINE. It was isolated originally from human URINE, but is found in most tissues of most VERTEBRATES. Plasminogen Activator, Urokinase-Type,U-Plasminogen Activator,Urinary Plasminogen Activator,Urokinase,Abbokinase,Kidney Plasminogen Activator,Renokinase,Single-Chain Urokinase-Type Plasminogen Activator,U-PA,Single Chain Urokinase Type Plasminogen Activator,U Plasminogen Activator,Urokinase Type Plasminogen Activator

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