Characterization of plasminogen activators from normal human breast and colon and from breast and colon carcinomas

116

Summary Matrix metalloproteinase (MMP) expression was investigated in patients with prostatic adenocarcinoma and benign prostatic hyperplasia (BPH). Forty-one men were studied: 26 had histologically proven prostate cancer, with 14 (54%) showing metastatic disease; 15 patients had BPH. Prostatic tissue was obtained from transurethral resection and needle core biopsies; gelatinolytic activity was determined by zymography. Seven gelatinolytic bands were detected, with molecular weights ranging from > 100 kilodalton (kDa) to 29 kDa. Nine of 14 patients (64%) with skeletal metastases had 92 kDa activity, present in only two of 12 patients (17%) with a negative bone scan, and absent in BPH. The 92 kDa gelatinolytic activity was expressed in 73% of aneuploid tumours compared with 20% of diploid tumours. A 97 kDa gelatinase was expressed in 80% of BPH samples and 23% of carcinoma patients. Enzyme bands of 72, 66 and 45 kDa were equally expressed in malignant tissue, irrespective of metastatic status, but were expressed in fewer BPH patients. The 97, 92, 66 and 45 kDa enzymes were identified as being pro-MMP-9 sequences by Western blotting, using a specific antibody directed against the pro sequence of the mature protein. MMP activity appeared to be increased in malignant prostatic tissue compared with BPH. Pro-MMP-9, in its 92 kDa form, was shown to be exclusively expressed by malignant prostatic tissue, and in particular by tumours that exhibited the aggressive and metastatic phenotype.Prostate cancer is the third most common malignancy in men in England and Wales, with over 9,000 new cases registered every year (Office of Population Censuses and Surveys, 1985).

Section: Discussionmentioning

confidence: 99%

Matrix metalloproteinase 9 expression in primary human prostatic adenocarcinoma and benign prostatic hyperplasia

Hamdy

Fadlon²,

Cottam³

et al. 1994

116

“…Several studies have been reported on the content of plasminogen activators in human breast tumours (Colombi et al, 1984;Evers et al, 1982;Tissot et al, 1984;Layer et al, 1987;Duffy et al, 1988) and elevated concentrations have been reported mainly to be due to an increase in the u-PA content (Evers et al, 1982;Layer et al, 1987). Duffy et al (1988) measured the t-PA concentration in breast tumour lysates and found that a high content of t-PA was associated with a good prognosis.…”

Section: Discussionmentioning

confidence: 99%

Tissue-type plasminogen activator in plasma from breast cancer patients determined by enzyme-linked immunosorbent assay

Grøndahl-Hansen

Bach²,

Munkholm-Larsen³

1990

Summary An enzyme-linked immunosorbent assay (ELISA) using monoclonal and polyclonal antibodies against t-PA was used to measure the concentration of tissue-type plasminogen activator (t-PA) in plasma from 34 healthy donors and 92 breast cancer patients with a varying extent of disease. The mean value of t-PA in plasma for the healthy donors was 2.4 ± 2.1 ng ml'-(s.d.). The mean value for the breast cancer patients was 5.3 ± 4.3 ng ml '. This increase was statistically significant at the 1% level. There was a positive correlation between the mean t-PA plasma concentration and the extent of disease in different groups of patients. Taking 5.0 ng ml-l as cut-off point, about 40% of the patients were positive, and 6% of the normal controls were false positive. Twenty-five per cent of the patients in complete remission, 28% of the patients with minimal tumour burden, 60% of the patients with moderate tumour burden, and 90% of the patients with massive tumour burden were positive. It is possible that the patients with an elevated plasma t-PA represent a group with a particularly bad prognosis.

“…uPA, Cath D and PAIs have been found in plasma (Saito et al, 1990;Freiss et al, 1988;Kruithof et al, 1987), and in many types of normal cells (Bernik et al, 1981;Jaffe, 1987;Chapman et al, 1982;Bergman et al, 1986;Keski-Oja et al, 1988;Wilson et al, 1987;Tissot et al, 1984;Wohlwend et al, 1987). However, we can consider that the tumour cells are the major producer.…”

Section: Patientsmentioning

confidence: 99%

“…The distribution of Cath D in human breast appears to be relatively specific for mammary epithelial cells and to be associated with tumour development (Garcia et al, 1984;Garcia et al, 1986). Besides, in culture, uPA, Cath D, and PAI-I are produced by many breast carcinoma cell lines (Tissot et al, 1984;Cajot et al, 1986;Quax et al, 1990;Briozzo et al, 1988). Moreover, Costantini et al (1991) have observed PAI-I in breast tumour cells using immunohistochemical technique.…”

Section: Patientsmentioning

confidence: 99%

“…They contribute to basement membrane and connective tissue degradation, allowing vascular endothelial crossover (for review: Mullins & Rohrlich, 1983;Tryggvason et al, 1987;Moscatelli & Rifkin, 1988;Gottesman, 1990). Diverse enzymes are produced in abundance by malignant cells and are implicated in tumour cell invasion: collagenases (for review : Liotta et al, 1982;Stetler-Stevenson, 1990); stromelysin (McDonnel & Matrisian, 1990); cathepsin B (Sloane et al, 1984;; cathepsin D (Maguchi et al, 1988;Rochefort et al, 1990); heparanase (Nakajima et al, 1987); urokinase type plasminogen activator (for review: Dano et al, 1985; Markus, 1988;Testa & Quigley, 1990).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Relationship between cathepsin D, urokinase, and plasminogen activator inhibitors in malignant vs benign breast tumours

Foucre

Bouchet²,

Hacène³

et al. 1991

Summary The concentrations of cathepsin D (Cath D), urokinase (uPA) and two plasminogen activator inhibitors (PAI-I and PAI-2) were analysed in the cytosols of 130 human mammary tumours (43 benign tumours and 87 primary and unilateral breast carcinomas). uPA, PAI-i and PAI-2 levels were measured by antigenic immunoassays and Cath D by immunoradiometric assay. The median levels of the four parameters were significantly higher in the malignant tumours than in the benign ones. Cath D and uPA increases were 4-fold and 5-fold respectively. PAI-I and PAI-2 increases were much more important, 74-fold and 29-fold respectively. In malignant tumours, median levels of Cath D and uPA did not vary according to classical prognostic factors (histologic grade, presence or absence of axillary lymph nodes, steroid receptors, UICC stage, tumour size, age, and menopausal status). However, PAI-I decreased in ER+ and PR+ tumours and PAI-2 increased in menopausal women's tumours. When Cath D, uPA, PAI-I and PAI-2 levels in malignant tumours were compared, positive correlations were found for all combinations. The implication of plasminogen activator inhibitors in the phenomenon was surprising and merits further investigation using tools other than global antigen measurements in tumours.