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Expression of 72 kilodalton type IV collagenase (gelatinase A) in benign and malignant ovarian tumors.

https://arctichealth.org/en/permalink/ahliterature23935
Source
Lab Invest. 1993 Sep;69(3):312-21
Publication Type
Article
Date
Sep-1993
Author
H. Autio-Harmainen
T. Karttunen
T. Hurskainen
M. Höyhtyä
A. Kauppila
K. Tryggvason
Author Affiliation
Department of Pathology, University of Oulu, Finland.
Source
Lab Invest. 1993 Sep;69(3):312-21
Date
Sep-1993
Language
English
Publication Type
Article
Keywords
Adenocarcinoma - enzymology - pathology
Antibodies, Monoclonal
Brenner Tumor - enzymology - pathology
Cystadenoma - enzymology - pathology
Female
Fibroma - enzymology - pathology
Gelatinase A
Gene Expression
Humans
Immunohistochemistry
In Situ Hybridization
Metalloendopeptidases - analysis - biosynthesis
Molecular Weight
Neoplasm Metastasis
Ovarian Cysts - enzymology - pathology
Ovarian Neoplasms - enzymology - pathology
RNA, Messenger - analysis - biosynthesis
Research Support, Non-U.S. Gov't
Abstract
BACKGROUND: 72 Kilodalton (kd) type IV collagenase is a matrix metalloproteinase that specifically cleaves type IV collagen molecules. The enzyme has been postulated to have an important role in the invasion and spread of malignant tumors. EXPERIMENTAL DESIGN: In situ hybridization was used to study the expression of the 72 kd type IV collagenase mRNA in 24 benign, 2 semimalignant, and 15 malignant ovarian tumors and in 5 metastases of ovarian serous adenocarcinomas. The results were correlated with the expression of the mRNA for the alpha 1(IV) chain of type IV collagen and with the corresponding immunohistochemical distribution of the enzyme. RESULTS: The results showed that the more malignant an ovarian tumor was, the more clearly mRNA expressions for both 72 kd type IV collagenase and the alpha 1(IV) chain could be detected in tumor cells. The expression of both types of mRNAs was localized within the cells of tumor stroma and occurred mainly in fibroblasts and vascular endothelial cells. Epithelial tumor cells only rarely expressed these mRNAs. Immunohistochemical stainings localized the 72 kd collagenase as well to the stromal cells as to the epithelial cells of both benign and malignant tumors. CONCLUSIONS: The findings indicate that genes for the 72 kd type IV collagenase and for its substrate are simultaneously active in the same cells of the tumor stroma. The difference in the in situ hybridization and immunohistochemical findings could be explained by a possible variation in the metabolic balance between synthesis and accumulation of the protein in different cell types. It can also be proposed that the activity of the 72 kd type IV collagenase would be mediated through a receptor-like mechanism present on epithelial cells which could bind the 72 kd type IV collagenase synthesized elsewhere. There is also a possibility that the gelatinolytic activity of the mesenchymally synthesized 72 kd type IV collagenase would be consumed to degrade extracellular matrix proteins other than basement membranes.
PubMed ID
8377473 View in PubMed
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Expression of the tissue metalloproteinase inhibitors TIMP-1 and TIMP-2 in malignant fibrous histiocytomas and dermatofibromas as studied by in situ hybridization and immunohistochemistry.

https://arctichealth.org/en/permalink/ahliterature22964
Source
Hum Pathol. 1996 Jan;27(1):42-9
Publication Type
Article
Date
Jan-1996
Author
T. Hurskainen
Y. Soini
A. Tuuttila
M. Höyhtyä
A. Oikarinen
H. Autio-Harmainen
Author Affiliation
Department of Pathology, Biochemistry, Dermatology, University of Oulu, Diabor OY, Finland.
Source
Hum Pathol. 1996 Jan;27(1):42-9
Date
Jan-1996
Language
English
Publication Type
Article
Keywords
Adult
Aged
Collagenases - antagonists & inhibitors
Female
Glycoproteins - analysis
Histiocytoma, Benign Fibrous - metabolism - pathology
Humans
Immunohistochemistry
In Situ Hybridization
Male
Metalloendopeptidases - antagonists & inhibitors
Middle Aged
Protease Inhibitors - analysis
Proteins - analysis
Research Support, Non-U.S. Gov't
Skin Neoplasms - metabolism - pathology
Tissue Inhibitor of Metalloproteinase-2
Tissue Inhibitor of Metalloproteinases
Abstract
The expression of tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) was studied in eight malignant fibrous histiocytomas (MFH) and in eight dermatofibromas (DF) using in situ hybridization methods (ISH). Immunohistochemical stainings were also performed using corresponding antibodies to TIMP-1 and TIMP-2. In ISH the neoplastic cells of MFHs showed a high level of expression for both TIMP-1 and TIMP-2 mRNAs. The cells usually expressed similarly both TIMPs, except for osteoclast-like giant cells, which showed a distinct signal for TIMP-2 but not for TIMP-1. A distinctly lower level of both TIMP-1 and TIMP-2 mRNAs was seen in DFs. Immunohistochemical stainings were concordant with the results obtained by ISH. The findings suggest that the behavior of MFHs and DFs is not directly or solely dependent on the quantity of type IV collagenase inhibitors. The increased TIMP synthesis in MFHs might represent a chaotic response of malignant cells to increased matrix degradation. Alternatively, it may reflect a deranged communication between type IV collagenases and TIMPs in malignant tissues.
PubMed ID
8543309 View in PubMed
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Matrix metalloproteinase-2 immunoreactive protein: a marker of aggressiveness in breast carcinoma.

https://arctichealth.org/en/permalink/ahliterature21465
Source
Cancer. 1998 Sep 15;83(6):1153-62
Publication Type
Article
Date
Sep-15-1998
Author
A. Talvensaari-Mattila
P. Pääkkö
M. Höyhtyä
G. Blanco-Sequeiros
T. Turpeenniemi-Hujanen
Author Affiliation
Department of Oncology and Radiotherapy, University of Oulu and Oulu University Hospital, Finland.
Source
Cancer. 1998 Sep 15;83(6):1153-62
Date
Sep-15-1998
Language
English
Publication Type
Article
Keywords
Age Factors
Analysis of Variance
Breast Neoplasms - chemistry - mortality - pathology
Carcinoma - chemistry - mortality - pathology
Female
Gelatinase A
Gelatinases - analysis
Humans
Immunohistochemistry
Metalloendopeptidases - analysis
Middle Aged
Neoplasm Proteins - analysis
Neoplasm Staging
Prognosis
Proportional Hazards Models
Receptors, Estrogen - analysis
Research Support, Non-U.S. Gov't
Abstract
BACKGROUND: Previous studies have shown that matrix metalloproteinase-2 (MMP-2) (a 72-kilodalton Type IV collagenase/gelatinase A) is associated with breast carcinoma, but to the authors' knowledge there are no reports showing that it is prognostic for overall survival. METHODS: Expression of the immunoreactive protein for MMP-2 was evaluated in tissue sections from primary breast carcinomas of 177 patients with a monoclonal antibody to MMP-2 using an immunohistochemical technique. RESULTS: Approximately 84% of the samples were MMP-2 positive, with 22% being strongly positive. Positive MMP-2 immunostaining was prognostic for shortened survival. After 10 years 56% of the patients with tumors that were strongly positive for MMP-2 were alive, whereas 88% of patients with an MMP-2 negative tumor and 70% of patients with weakly or moderately positive tumors were still alive (chi-square test = 7.4; P
PubMed ID
9740080 View in PubMed
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Matrix metalloproteinase 2 immunoreactive protein appears early in cervical epithelial dedifferentiation.

https://arctichealth.org/en/permalink/ahliterature21208
Source
Gynecol Oncol. 1999 Mar;72(3):306-11
Publication Type
Article
Date
Mar-1999
Author
A. Talvensaari
M. Apaja-Sarkkinen
M. Höyhtyä
A. Westerlund
U. Puistola
T. Turpeenniemi
Author Affiliation
Department of Oncology and Radiotherapy, University Hospital of Oulu, Oulu, Finland.
Source
Gynecol Oncol. 1999 Mar;72(3):306-11
Date
Mar-1999
Language
English
Publication Type
Article
Keywords
Carcinoma, Squamous Cell - enzymology - pathology
Cell Transformation, Neoplastic
Cervical Intraepithelial Neoplasia - enzymology - pathology
Epithelial Cells - enzymology
Female
Gelatinase A
Gelatinases - metabolism
Humans
Immunohistochemistry
Metalloendopeptidases - metabolism
Neoplasm Staging
Uterine Cervical Neoplasms - enzymology - pathology
Abstract
OBJECTIVE: Expression of the immunoreactive protein of matrix metalloproteinase 2 (MMP-2) was studied in cervical tumors representing various stages of cell atypia and differentiation. In this study, we evaluated whether the expression of MMP-2 is an early or late event in the process of dedifferentiation and cancer progression. METHODS: Paraffin tissue sections from 60 cervical neoplasias including 38 cervical intraepithelial neoplasias (CINs) and 22 early-stage (stage IB and IIA) squamous cervical carcinomas were studied with respect to the expression of MMP-2 protein by using immunoperoxidase staining. RESULTS: The staining pattern of MMP-2 in the CIN lesions usually differed from that in squamous carcinoma. Latent MMP-2 protein localized, in most of the cases, to the periphery of the CIN cells, but was diffuse in the cytoplasm of the carcinoma cells. No correlation was found between overexpression of MMP-2 protein and degree of dysplasia, nor was there any association between MMP-2 and human papillomavirus (HPV). High scores for MMP-2 were observed only in histologically higher-grade early-stage cervical carcinomas. The lymph node metastases derived from high-MMP-2-score primary tumors were also positive for MMP-2. No correlation between MMP-2 staining and clinical course or prognosis was found. CONCLUSIONS: MMP-2 expression is an early event during dedifferentiation and malignant transformation in cervical neoplasias. The pattern of staining is different in CIN than in squamous carcinoma cells, in which overexpression may correlate with the degree of anaplasia.
PubMed ID
10053100 View in PubMed
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Matrix metalloproteinase-2 (MMP-2) immunoreactive protein--a new prognostic marker in uveal melanoma?

https://arctichealth.org/en/permalink/ahliterature20953
Source
J Pathol. 1999 May;188(1):56-62
Publication Type
Article
Date
May-1999
Author
A. Väisänen
M. Kallioinen
K. von Dickhoff
L. Laatikainen
M. Höyhtyä
T. Turpeenniemi-Hujanen
Author Affiliation
Department of Oncology and Radiotherapy, University Hospital of Oulu, Finland.
Source
J Pathol. 1999 May;188(1):56-62
Date
May-1999
Language
English
Publication Type
Article
Keywords
Adult
Aged
Aged, 80 and over
Female
Gelatinase A - analysis
Humans
Immunohistochemistry
Male
Melanoma - chemistry - mortality - secretion
Middle Aged
Prognosis
Research Support, Non-U.S. Gov't
Survival Rate
Tumor Markers, Biological - analysis
Uveal Neoplasms - chemistry - mortality
Abstract
Uveal melanoma is the most common primary intraocular tumour. Once haematogenous metastasis has occurred, there is no cure for the disease and there is an obvious need for new biological prognostic markers to estimate the risk of metastasis. In this study, the expression of matrix metalloproteinase-2 (MMP-2) was characterized immunohistochemically in 29 human uveal melanomas. Enzyme-linked immunoassays and gelatin zymographies were assessed in order to quantify the expression of gelatinases A and B, as well as the tissue inhibitor of metalloproteinases (TIMPs), in the vitreous body. A total of 49 per cent of the uveal melanomas displayed a positive immunoreaction for MMP-2 in melanoma cells, the epithelioid cells showing the most frequent staining. There was no correlation between the positivity of MMP-2 staining and the size of the primary tumour, gender or age. The expression of MMP-2 was associated with a dismal prognosis: the 5-year overall survival rate for MMP-2-positive cases was significantly inferior to that of the MMP-2 negative cases, 49 per cent vs. 86 per cent, respectively (p=0.02). A patient group at high risk of metastatic disease was identified; only 38 per cent of patients with a MMP-2-positive non-spindle cell uveal melanoma survived for 5 years. The analyses of MMPs or TIMPs in the vitreous body had no prognostic value. Positive immunostaining for MMP-2 was observed in the retinal pigment epithelium, corneal epithelium, and fibroblasts in the ciliary body and choroid. It is concluded that immunohistochemical analysis of MMP-2 may help to predict a risk of metastasis in uveal melanoma.
PubMed ID
10398141 View in PubMed
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Matrix metalloproteinase 2 (MMP-2) immunoreactive protein is associated with poor grade and survival in brain neoplasms.

https://arctichealth.org/en/permalink/ahliterature20350
Source
J Neurooncol. 2000;46(1):81-90
Publication Type
Article
Date
2000
Author
J. Jäälinojä
R. Herva
M. Korpela
M. Höyhtyä
T. Turpeenniemi-Hujanen
Author Affiliation
Department of Oncology and Radiotherapy, University of Oulu, Oulu University Hospital, Finland.
Source
J Neurooncol. 2000;46(1):81-90
Date
2000
Language
English
Publication Type
Article
Keywords
Adult
Brain Neoplasms - enzymology - pathology
Female
Gelatinase A - metabolism
Humans
Immunohistochemistry - methods
Male
Middle Aged
Staining and Labeling
Survival Analysis
Abstract
Matrix metalloproteinases play an important role in the invasion of tumor cells and the progression of cancer. The 72 kDa type IV collagenase, a matrix metalloproteinase 2 (MMP-2) has been shown to contribute to the invasion and metastasis in diverse malignant neoplasms. OBJECT: To elaborate the potential role of MMP-2 in brain tumor invasion we studied the expression and localization of this enzyme protein in 101 brain tumors representing different types of brain neoplasms. For the first time, we also correlated the expression of MMP-2 protein to patient survival. METHODS: Using immunohistochemistry and a monoclonal antibody specific for MMP-2 we found that MMP-2 protein was primarily localized in tumor cells and vasculature cells as well as inflammatory cells. The expression of MMP-2 was absent or negligible in benign tumors (pilocytic astrocytoma and meningioma). Thirty-three percent (6/18) of astrocytomas, 38% (3/8) of anaplastic astrocytomas, 14% (1/7) of anaplastic oligodendrogliomas, 54% (19/35) of glioblastomas and 100% (6/6) of metastatic brain tumors were positive for MMP-2. A correlation between MMP-2 expression and survival was found in malignant brain tumors. The mean survival of patients with an MMP-2 negative tumor was 36 months, when it was only 7-14 months in patients with an MMP-2 positive tumor. CONCLUSIONS: Our data suggest that MMP-2 is associated with histological malignancy and poor survival in brain tumors.
PubMed ID
10896208 View in PubMed
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Modulation of skin collagen metabolism by irradiation: collagen synthesis is increased in irradiated human skin.

https://arctichealth.org/en/permalink/ahliterature20457
Source
Br J Dermatol. 2000 May;142(5):874-80
Publication Type
Article
Date
May-2000
Author
R. Riekki
A. Jukkola
M L Sassi
M. Höyhtyä
M. Kallioinen
J. Risteli
A. Oikarinen
Author Affiliation
Departments of Dermatology and Oncology, University of Oulu, FIN 90220 Oulu, Finland.
Source
Br J Dermatol. 2000 May;142(5):874-80
Date
May-2000
Language
English
Publication Type
Article
Keywords
Adult
Aged
Blister - blood
Breast Neoplasms - radiotherapy
Collagen - biosynthesis
Comparative Study
Female
Humans
Immunohistochemistry
Middle Aged
Procollagen - analysis - metabolism
Reference Values
Research Support, Non-U.S. Gov't
Skin - chemistry - metabolism - radiation effects
Tissue Inhibitor of Metalloproteinase-1 - analysis - blood
Tissue Inhibitor of Metalloproteinase-2 - analysis - blood
Abstract
Radiation-induced fibrosis is a common side-effect of cancer treatment. The pathophysiological events leading to fibrosis are not known in detail. We analysed the effect of therapeutic irradiation on human skin collagen synthesis, skin thickness, gelatinases and their inhibitors. Twenty randomly chosen women who had been treated for breast cancer with surgery and radiation therapy participated in the study. In each patient, the irradiated skin area was compared with a corresponding non-treated skin area. Suction blister fluid (SBF) and serum samples were analysed for the aminoterminal propeptides of type I and type III procollagens (PINP and PIIINP), tissue inhibitors of matrix metalloproteinases (MMPs) 1 and 2 (TIMP-1 and TIMP-2) and MMP-9 and MMP-2/TIMP-2 complex. Skin biopsies were analysed for PINP and immunohistochemical staining was used for PIIINP. In irradiated skin, PINP, PIIINP, TIMP-1 and MMP-2/TIMP-2 complex levels in SBF and the number of PINP-positive fibroblasts in tissue sections were significantly higher in comparison with non-treated skin. The levels of TIMP-2 in irradiated and non-irradiated skin were similar. MMP-9 could not be detected in SBF with the assay used. The serum levels of MMP-9 were higher in the treated subjects than the reference values. The serum values of PINP, PIIINP, TIMP-1, TIMP-2 and MMP-2/TIMP-2 complex were not significantly affected. These results indicate increased local collagen synthesis and accumulation of connective tissue in irradiated skin. The marked upregulation of collagen synthesis as a result of irradiation offers a possibility to treat this complication with compounds such as topical steroids which downregulate collagen synthesis.
PubMed ID
10809842 View in PubMed
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mRNA expressions of TIMP-1, -2, and -3 and 92-KD type IV collagenase in early human placenta and decidual membrane as studied by in situ hybridization.

https://arctichealth.org/en/permalink/ahliterature64406
Source
J Histochem Cytochem. 1996 Dec;44(12):1379-88
Publication Type
Article
Date
Dec-1996
Author
T. Hurskainen
M. Höyhtyä
A. Tuuttila
A. Oikarinen
H. Autio-Harmainen
Author Affiliation
Department of Pathology, University of Oulu, Finland.
Source
J Histochem Cytochem. 1996 Dec;44(12):1379-88
Date
Dec-1996
Language
English
Publication Type
Article
Keywords
Collagenases - genetics
Female
Humans
Immunohistochemistry
In Situ Hybridization
Placenta - enzymology - metabolism
Pregnancy
Protease Inhibitors - metabolism
RNA, Messenger - genetics - metabolism
Research Support, Non-U.S. Gov't
Abstract
Cytotrophoblasts of early placenta invade the decidual membrane, gestational endometrium, and spiral arteries during early pregnancy. Unlike tumor invasion, this physiological invasion is well controlled, although its molecular mechanisms are largely unknown. We have previously shown that cytotrophoblasts synthesize significant mRNAs for 72-KD Type IV collagenase, laminin, and Type IV collagen, proteins implicated in extracellular matrix turnover and migration. In this study we used in situ hybridization and immunohistochemistry to investigate the mRNA expression pattern of 92-KD Type IV collagenase and the matix metalloproteinase inhibitors TIMP-1, TIMP-2, and TIMP-3 in early human placenta and decidual membrane. mRNAs for 92-KD Type IV collagenase, TIMP-1, TIMP-2, and TIMP-3 were found in the cells of cytotrophoblastic columns, the endothelial and fibroblastic stromal cells of villi, and the large decidualized cells of decidual membrane. TIMP-1 expression was notably accentuated in the fibroblasts of fibrotic villi. In the decidual membrane, the signals for 92-KD Type IV collagenase and TIMP-1 mRNA were particularly strong around the glandular structures. The trophoblastic epithelium of villi and the epithelial cells of decidual glands showed a signal for 92-KD Type IV collagenase and TIMP-2, but not for TIMP-1 or TIMP-3. The coincidental expression of the proteolytic 92-KD Type IV collagenase and inhibitors TIMP-1, TIMP-2, and TIMP-3 generally in the same cells suggests that the activity of 92-KD Type IV collagenase, which is regulated by TIMPs, plays an important role in placental tissue organization and in the invasion of trophoblastic cells into the uterine wall.
PubMed ID
8985130 View in PubMed
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8 records – page 1 of 1.