Immunohistochemical localization of urokinase-type plasminogen activator, type-1 plasminogen-activator inhibitor, urokinase receptor and α2-macroglobulin receptor in human breast carcinomas

Christensen, Lise; Simonsen, Anna Carina Wiborg; Heegaard, Christian W.; Moestrup, Søren K.; Andersen, Johan A.; Andreasen, Peter A.

doi:10.1002/(sici)1097-0215(19960516)66:4<441::aid-ijc6>3.0.co;2-w

Cited by 95 publications

(54 citation statements)

References 38 publications

(20 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Significant correlations between IHC scores and ELISA values were found for uPA in primary breast carcinoma lesions (Jänicke et al, 1990) and colon carcinoma (Sier et al, 1991), for uPA and PAI-1 in cervical cancer of the uterus (Kobayashi et al, 1994) and lymph node metastases of breast cancer but not in primary breast cancer (Christensen et al, 1996), and for PAI-1 but not for uPAR in non-small-cell lung cancer . Some of the above mentioned studies described IHC on paraffin sections (Jänicke et al, 1990;Sier et al, 1991;Kobayashi et al, 1994) whereas others, like us, performed IHC on frozen tissue (Christensen et al, 1996;Pappot et al, 1997). Correlation coefficients reported range from 0.49 to 0.80.…”

Section: Discussionmentioning

confidence: 99%

Comparison of immunohistochemistry with immunoassay (ELISA) for the detection of components of the plasminogen activation system in human tumour tissue

et al. 1999

View full text Add to dashboard Cite

Enzyme-linked immunosorbent assay (ELISA) methods and immunohistochemistry (IHC) are techniques that provide information on protein expression in tissue samples. Both methods have been used to investigate the impact of the plasminogen activation (PA) system in cancer. In the present paper we first compared the expression levels of uPA, tPA, PAI-1 and uPAR in a compound group consisting of 33 cancer lesions of various origin (breast, lung, colon, cervix and melanoma) as quantitated by ELISA and semi-quantitated by IHC. Secondly, the same kind of comparison was performed on a group of 23 melanoma lesions and a group of 28 breast carcinoma lesions. The two techniques were applied to adjacent parts of the same frozen tissue sample, enabling the comparison of results obtained on material of almost identical composition. Spearman correlation coefficients between IHC results and ELISA results for uPA, tPA, PAI-1 and uPAR varied between 0.41 and 0.78, and were higher for the compound group and the breast cancer group than for the melanoma group. Although a higher IHC score category was always associated with an increased median ELISA value, there was an overlap of ELISA values from different scoring classes. Hence, for the individual tumour cases the relation between ELISA and IHC is ambiguous. This indicates that the two techniques are not directly interchangeable and that their value for clinical purposes may be different. © 1999 Cancer Research Campaign

show abstract

Section: Discussionmentioning

confidence: 99%

Comparison of immunohistochemistry with immunoassay (ELISA) for the detection of components of the plasminogen activation system in human tumour tissue

et al. 1999

View full text Add to dashboard Cite

show abstract

“…While it functionally stimulates metastasis, it also acts as a mitogen for cancer cells and promotes angiogenesis [63], and induces stromal proliferation in tumors. In turn, the stromal fibroblasts produce proteases that aid in the degradation of the extracellular matrix [64][65][66].…”

Section: Validation Of the Lc-ms Datamentioning

confidence: 99%

Identification of Differentially Secreted Biomarkers Using LC-MS/MS in Isogenic Cell Lines Representing a Progression of Breast Cancer

et al. 2007

View full text Add to dashboard Cite

Proteins secreted (the secretome) from cancer cells are potentially useful as biomarkers of the disease. Using LC-MS/MS, the secreted proteomes from a series of isogenic breast cancer cell lines varying in aggressiveness were analyzed by mass spectrometry: non-tumorigenic MCF10A, premalignant/ tumorigenic MCF10AT, tumorigenic/locally invasive MCF10 DCIS.com and tumorigenic/ metastatic MCF 10CA cl. D. Proteomes were obtained from conditioned serum-free media, partially fractionated using a small reverse phase C2 column and digested with trypsin for analysis by LC-MS/MS, using a method previously shown to give highly enriched secreted proteomes (Mbeunkui, et. al., J. Prot. Res. 5, 899-906 2006). The search files produced from 5 analyses (3 separate preparations) were combined for database searching (Mascot) which produced a list of over 250 proteins from each cell line. The aim was to discover highly secreted proteins which changed significantly in abundance corresponding with aggressiveness. The most apparent changes were observed for alpha-1-antichymotrypsin and galectin-3-binding protein which were highly secreted proteins from MCF10 DCIS.com and MCF10CA cl. D, yet undetected in the MCF10A and MCF10AT cell lines. Other proteins showing increasing abundance in the more aggressive cell lines included alpha-1-antitrypsin, cathepsin D and lysyl oxidase. The S100 proteins, often associated with metastasis, showed variable changes in abundance. While the cytosolic proteins were low (e.g. actin and tubulin), there was significant secretion of proteins often associated with the cytoplasm. These proteins were all predicted as products of non-classical secretion (SecretomeIP, Center for Biological Sequence Analysis). The LC-MS/MS results were verified for five selected proteins by western blot analysis, and the relevance of other significant proteins is discussed. Comparisons with two other aggressive breast cancer cell lines are included and the protein with consistent association with aggressiveness in all lines, and in unrelated cancer cells, was the galectin-3-binding protein which has been associated with breast, prostate and colon cancer earlier, supporting the approach and findings. This analysis of an isogenic series of cell lines suggests the potential usefulness of the secretome for identifying prospective markers for the early detection and aggressiveness/progression of cancer.

show abstract

“…Fourth, PAI-1 may have a multitude of functions in breast tumours, angiogenesis only being one among several. The latter hypothesis is favoured by the immunohistochemical localization of PAI-1 to several cell types in breast tumours, including not only endothelial cells but also fibroblasts and cancer cells (Christensen et al, 1996).…”

Section: Molecular and Cellular Pathologymentioning

confidence: 99%

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

et al. 2003

View full text Add to dashboard Cite

Tumour angiogenesis and the levels of plasminogen activator inhibitor type 1 (PAI-1) are both informative prognostic markers in breast cancer. In cell cultures and in animal model systems, PAI-1 has a proangiogenic effect. To evaluate the interrelationship of angiogenesis and the PAI-1 level in breast cancer, we have evaluated the prognostic value of those factors in a total of 228 patients with primary, unilateral, invasive breast cancer, evaluated at a median follow-up time of 12 years. Microvessels were immunohistochemically stained by antibodies against CD34 and quantitated by the Chalkley counting technique. The levels of PAI-1 and its target proteinase uPA in tumour extracts were analysed by ELISA. The Chalkley count was not correlated with the levels of uPA or PAI-1. High values of uPA, PAI-1, and Chalkley count were all significantly correlated with a shorter recurrence-free survival and overall survival. In the multivariate analysis, the uPA level did not show independent prognostic impact for any of the analysed end points. In contrast, the risk of recurrence was independently and significantly predicted by both the PAI-1 level and the Chalkley count, with a hazard ratio (95% CI) of 1.6 (1.01-2.69) and 1.4 (1.02-1.81), respectively. For overall survival, the Chalkley count, but not PAI-1, was of significant independent prognostic value. The risk of death was 1.7 (1.30-2.15) for Chalkley counts in the upper tertile compared to the lower one. We conclude that the PAI-1 level and the Chalkley count are independent prognostic markers for recurrence-free survival in patients with primary breast cancer, suggesting that the prognostic impact of PAI-1 is not only based on its involvement in angiogenesis.

show abstract

Immunohistochemical localization of urokinase-type plasminogen activator, type-1 plasminogen-activator inhibitor, urokinase receptor and α2-macroglobulin receptor in human breast carcinomas

Cited by 95 publications

References 38 publications

Comparison of immunohistochemistry with immunoassay (ELISA) for the detection of components of the plasminogen activation system in human tumour tissue

Comparison of immunohistochemistry with immunoassay (ELISA) for the detection of components of the plasminogen activation system in human tumour tissue

Identification of Differentially Secreted Biomarkers Using LC-MS/MS in Isogenic Cell Lines Representing a Progression of Breast Cancer

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

Contact Info

Product

Resources

About