Increase in levels of plasminogen activator and type-1 plasminogen activator inhibitor in human breast cancer: Possible roles in tumor progression and metastasis

Sumiyoshi, Kenichi; Baba, Shigeaki; Sakaguchi, Shukichi; Urano, Tetsumei; Takada, Yumiko; Takada, Akikazu

doi:10.1016/0049-3848(91)90270-7

Cited by 51 publications

(23 citation statements)

References 30 publications

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“…Kennedy et al (1998) described positive stromal cells as fibroblasts, myofibroblasts, and macrophage-like cells, and with double staining they identified uPA-positive macrophages but no uPA-positive vessels. In contrast, our results strongly disagree with those of Jänicke et al (1991), Sumiyoshi et al (1991), Jankun et al (1993), Del Vecchio et al (1993), and Damjanovich et al (1994), who all found that uPA is exclusively or mainly located in cancer cells, and our results also disagree with those reported by Costantini et al (1991Costantini et al ( , 1996, Carriero et al (1994), Christensen et al (1996), and Dublin et al (2000), who found substantial staining of both cancer cells and stromal cells.…”

Section: Nielsen Et Alcontrasting

confidence: 57%

“…Each of these four uPA-antibodies have previously been used in immunohistochemical studies of uPA in breast cancer (Carriero et al, 1994;Christensen et al, 1996;Del Vecchio et al, 1993;Jänicke et al, 1991;Jankun et al, 1993;Kennedy et al, 1998;Sumiyoshi et al, 1991). We also included two additional control mAb of irrelevant specificity (anti-hirudin and antiovalbumin).…”

Section: Different Upa Antibodiesmentioning

confidence: 99%

“…Because detergent wash may not have been used in some of the studies in which uPA immunostaining has been found in breast cancer cells (Jänicke et al, 1991;Jankun et al, 1993;Sumiyoshi et al, 1991), we tested the effect of omission of detergent. These experiments were done with paraffin sections that had been formalin fixed for 24 hours at room temperature to mimic the conditions that exist for routine stainings in pathology departments and in the above-cited uPA staining studies.…”

Section: Detergent Washmentioning

confidence: 99%

“…Until now, however, this issue has not been clarified, despite several immunohistochemical studies (Carriero et al, 1994;Christensen et al, 1996;Costantini et al, 1991Costantini et al, , 1996Damjanovich et al, 1994;Del Vecchio et al, 1993;Dublin et al, 2000;Jänicke et al, 1991;Jankun et al, 1993;Kennedy et al, 1998;Sumiyoshi et al, 1991;Visscher et al, 1993Visscher et al, , 1995. Many groups report that the uPA immunostaining is localized exclusively or mainly in the cancer cells in contrast to the above discussed localization of uPA mRNA (Costantini et al, 1991(Costantini et al, , 1996Damjanovich et al, 1994;Del Vecchio et al, 1993;Jänicke et al, 1991;Jankun et al, 1993;Sumiyoshi et al, 1991). In other studies, uPA immunostaining was mainly found in stromal cells (Kennedy et al, 1998;Visscher et al, 1993Visscher et al, , 1995, whereas some authors found substantial staining of both cancer cells and stromal cells (Carriero et al, 1994;Christensen et al, 1996;Dublin et al, 2000).…”

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confidence: 99%

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Urokinase Plasminogen Activator Is Localized in Stromal Cells in Ductal Breast Cancer

Nielsen¹,

Sehested²,

Duun

et al. 2001

Laboratory Investigation

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SUMMARY:Urokinase plasminogen activator (uPA) regulates a proteolytic cascade that facilitates cancer invasion through degradation of the extracellular matrix, and high levels of uPA in human breast cancer tissue correlate with poor prognosis. We previously found that, in ductal breast cancer, uPA mRNA is highly expressed by myofibroblasts surrounding invasively growing cancer cells. However, the localization of uPA protein has not been settled in the published literature. Because uPA is a secreted molecule, it could conceivably be localized differently from its mRNA. We have studied the localization of uPA immunoreactivity in detail. Twenty-five cases of invasive ductal carcinoma were analyzed with three different uPA antibody preparations, all of which gave an essentially identical stromal staining pattern. Using double immunofluorescence, we identified uPA immunoreactivity in myofibroblasts and macrophages in all cases examined. Additionally, in approximately half of the tumors, we saw uPA staining of endothelial cells. In 3 of the 25 cases, a small subpopulation of the cancer cells was uPA-positive. We conclude that uPA immunoreactivity is almost exclusively associated with stromal cells, which thus play a major role in generation of proteolytic activity in ductal breast cancer. (Lab Invest 2001, 81:1485-1501.

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Section: Nielsen Et Alcontrasting

confidence: 57%

Section: Different Upa Antibodiesmentioning

confidence: 99%

Section: Detergent Washmentioning

confidence: 99%

mentioning

confidence: 99%

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Urokinase Plasminogen Activator Is Localized in Stromal Cells in Ductal Breast Cancer

Nielsen¹,

Sehested²,

Duun

et al. 2001

Laboratory Investigation

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“…Many human tumour types have been found to have increased levels of u-PA, u-PA receptor, PAI-l and/or PAI-2, and decreased levels of t-PA compared with their corresponding normal tissue counterparts (Sier et al, 1991;1993a, b;Sumiyoshi et al, 1991;Tanaka et al, 1991;Nakamura et al, 1992;de Vries et al, 1994). These changes found in the plasminogen activation system were not only contributing to tumour invasion and metastasis but were also of particular clinical relevance because of their impact on prognosis.…”

mentioning

confidence: 99%

Contribution of plasminogen activators and their inhibitors to the survival prognosis of patients with Dukes' stage B and C colorectal cancer

Ganesh

Sier²,

Heerding³

et al. 1997

Br J Cancer

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Summary Despite the advances in pre-, peri-and post-operative medical care of colorectal carcinoma patients, the prognosis has improved only marginally over recent decades. Thus, additional prognostic indicators would be of great clinical value to select patients for adjuvant therapy. In previous studies we found that colorectal carcinomas have a marked increase of the urokinase-type of plasminogen activator (u-PA), and the inhibitors PAI-1 and PAI-2, whereas the tissue-type plasminogen activator (t-PA) is found to be decreased in comparison with adjacent normal mucosa. In the present study we evaluated the prognostic value of several plasminogen activation parameters, determined in both normal and carcinomatous tissue from colorectal resection specimens, for overall survival of 136 Dukes' stage B and C colorectal cancer patients, in relation to major clinicopathological parameters. Uni-and multivariate analyses indicated that a high PAI-2 antigen level in carcinoma, a low t-PA activity and antigen level and a high u-PA/t-PA antigen ratio in adjacent normal mucosa are significantly associated with a poor overall survival. A high ratio of u-PA antigen in the carcinomas and t-PA antigen in normal mucosa, i.e. u-PA(C)/t-PA(N), was found to be predictive of a poor overall survival as well. All these parameters were found to be prognostically independent of the clinicopathological parameters. Multivariate analysis of combinations of these prognostically significant plasminogen activation parameters revealed that they are important independent prognostic indicators and have in fact a better prognostic value than their separate components. Based on these combined parameters, subgroups of patients with Dukes' stage B and C colorectal cancer could be identified as having either a high or a low risk regarding overall survival. In conclusion, these findings emphasize the relevance of the intestinal plasminogen activation system for survival prognosis of patients with colorectal cancer and, in the future, might constitute a patient selection criterion for adjuvant therapy.

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Prognostic value of the plasminogen activation system in patients with gastric carcinoma

Ganesh¹,

Sier²,

Heerding³

et al. 1996

Cancer

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Increase in levels of plasminogen activator and type-1 plasminogen activator inhibitor in human breast cancer: Possible roles in tumor progression and metastasis

Cited by 51 publications

References 30 publications

Urokinase Plasminogen Activator Is Localized in Stromal Cells in Ductal Breast Cancer

Urokinase Plasminogen Activator Is Localized in Stromal Cells in Ductal Breast Cancer

Contribution of plasminogen activators and their inhibitors to the survival prognosis of patients with Dukes' stage B and C colorectal cancer

Prognostic value of the plasminogen activation system in patients with gastric carcinoma

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