Independent prognostic value of angiogenesis and the level of plasminogen activator inhibitor type 1 in breast cancer patients

Hansen, Steinbjørn; Overgaard, Jens; Rose, Carsten; Knoop, Ann; Laenkholm, Anne Vibeke; Andersen, Jørn; Fb, Sørensen; Andreasen, P.A.

doi:10.1038/sj.bjc.6600662

Cited by 30 publications

(12 citation statements)

References 33 publications

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“…PAI-1 secreted by endothelial cells may protect the basement membrane around new vessels against proteolysis and thus promote angiogenesis. The prognostic values of angiogenesis, as evaluated by the Chalkley count, and of the PAI-1 level in breast tumour extracts are independent [72]. This result does not support an idea of the only or main function of PAI-1 in breast tumours being one of promoting angiogenesis, but is certainly consistent with the idea that it is one function among others (Fig.…”

Section: Pai-1 In the Stroma Of Human And Experi-mental Tumourssupporting

confidence: 78%

PAI-1 - A Potential Therapeutic Target in Cancer

Andreasen

2007

CDT

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Beginning in the early 90 es, evidence has been accumulating that a high level of plasminogen activator inhibitor-1 (PAI-1) protein in extracts of human primary malignant tumours is one of the most informative biochemical markers of a poor prognosis in several human cancer types. This observation has given the impetus to numerous studies of the role of PAI-1 in tumour growth, invasion, and metastasis. Recent mapping of cell types expressing PAI-1 in human tumours and studies with tumours growing on mice with targeted disruption of the PAI-1 gene have given results consistent with the idea that PAI-1 expressed by stromal fibroblasts and endothelial cells promotes tumour growth and spread. PAI-1 expressed by these cells therefore seems to be a potential therapeutic target in cancer. Confusingly, however, PAI-1 is also expressed by other cell types in tumours, and in some cancer types, the predominant PAI-1-expressing cells are the malignant epithelial cells themselves. Adding to the complexity is the fact that PAI-1 is not only a plasminogen activator inhibitor, but also engages in other molecular interactions, i.e., binds the extracellular matrix protein vitronectin and endocytosis receptors of the low density lipoprotein receptor family. Further progress towards the utilisation of PAI-1 as a therapeutic target in cancer will depend on understanding the role of PAI-1 expressed by different cell types in tumours and on development of compounds inhibiting separately each molecular interaction of PAI-1. The eventual use of PAI-1 as a therapeutic target will depend on mapping PAI-1 levels and PAI-1 expressing cell types in tumours of individual patients.

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Section: Pai-1 In the Stroma Of Human And Experi-mental Tumourssupporting

confidence: 78%

PAI-1 - A Potential Therapeutic Target in Cancer

Andreasen

2007

CDT

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“…However, contrary to our hypothesis, breast and abdominal adipose MSCs were roughly similar in terms of expression of a panel of genes, with the exception of IL-1b; that was higher in abdominal adipose MSCs. Both adipose MSCs upregulated FGF2, SERPINE1, VEGFA, and VEGFC in macrophages after coculture, and those genes have been associated with progression of breast cancer in previous reports (19, 20). However, there were no statistically significant differences between breast adipose MSC cocultured macrophages and abdominal adipose MSC cocultured macrophages (Figure 2).…”

Section: Discussionsupporting

confidence: 51%

Comparison of Breast and Abdominal Adipose Tissue Mesenchymal Stromal/Stem Cells in Support of Proliferation of Breast Cancer Cells

Kim¹,

Escalante²,

Dollar³

et al. 2013

Cancer Investigation

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In this study, we compared MSCs from breast and abdominal tissue in terms of their expression of genes deemed important in the support of breast cancer growth and their effect on gene profile of macrophages after coculture. In addition, we investigated the role of MSCs, alone or in combination with macrophages, on proliferation of breast cancer cell lines. Our results show that MSCs derived from breast and abdominal adipose tissues have a comparable gene expression profile, have similar effect on gene expression of macrophages, and are comparable in supporting breast cancer cell line proliferation.

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“…It is relevant to note that the prognostic values of estimates of angiogenesis and the PAI-1 level in breast cancer were recently reported to be independent. 52 In all 25 cases, PAI-1 was detected in fibroblast-like cells, most of which were found to be ␣-SMA-positive. ␣-SMA is not confined to myofibroblasts but is also expressed in vascular smooth muscle cells and myoepithelial cells.…”

Section: Discussionmentioning

confidence: 99%

The Myofibroblast Is the Predominant Plasminogen Activator Inhibitor-1-Expressing Cell Type in Human Breast Carcinomas

Offersen

Nielsen²,

Høyer‐Hansen³

et al. 2003

The American Journal of Pathology

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The tumor level of plasminogen activator inhibitor-1 (PAI-1) is an informative biochemical marker of a poor prognosis in several cancer types. However, the tumor biological functions of PAI-1 and the identity of PAI-1-expressing cells are controversial. With the aim of immunohistochemically localizing PAI-1 in formalin-fixed, paraffin-embedded invasive ductal breast carcinoma samples, we raised new polyclonal antibodies against PAI-1 from different expression systems. The antibodies were affinity purified by absorption on immobilized preparations of PAI-1 different from those used for immunization. The specificity of the antibodies was ensured by immunoblotting analysis. In immunohistochemistry, the staining pattern obtained with the antibodies showed a good correlation with the PAI-1 mRNA expression pattern. In all 25 cases analyzed, PAI-1 immunoreactivity was predominantly localized in fibroblast-like cells. Double-immunofluorescence analyses showed co-expression of PAI-1 and ␣-smooth muscle actin in these cells, suggesting that they are myofibroblasts. PAI-1 was also seen in some myoepithelial cells surrounding occasional foci of ductal carcinoma in situ (9 of 25), some endothelial cells (8 of 25), some cancer cells (3 of 25), and some mast cells (6 of 25). In conclusion, we have provided a robust immunohistochemical procedure for detection of PAI-1 and shown that the majority of the PAI-1-expressing cells in invasive ductal breast carcinomas are myofibroblasts.

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Independent prognostic value of angiogenesis and the level of plasminogen activator inhibitor type 1 in breast cancer patients

Cited by 30 publications

References 33 publications

PAI-1 - A Potential Therapeutic Target in Cancer

PAI-1 - A Potential Therapeutic Target in Cancer

Comparison of Breast and Abdominal Adipose Tissue Mesenchymal Stromal/Stem Cells in Support of Proliferation of Breast Cancer Cells

The Myofibroblast Is the Predominant Plasminogen Activator Inhibitor-1-Expressing Cell Type in Human Breast Carcinomas

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