Influence of preoperative core biopsies on uPA/PAI-1 expression in breast cancer tissue

Haas, Susanne; Park, Tjoung‐Won; Hahne, Jens C.; Fischer, Hans‐Peter

doi:10.1007/s00428-007-0563-8

Cited by 15 publications

(11 citation statements)

References 15 publications

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“…10,19,103-113. activator (uPA) complex than in intact parts of the tumor. 117 Tumor seeding in the biopsy tract is very rare, except for sarcomas. Nevertheless, surgeons are well aware of the preclinical evidence for proinvasive and prometastatic potential of wound reactions.…”

Section: Characterization and Origin Of A Myofibroblastmentioning

confidence: 99%

Stromal myofibroblasts are drivers of invasive cancer growth

Wever¹,

Demetter²,

Mareel³

et al. 2008

Intl Journal of Cancer

631

601

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Tissue integrity is maintained by the stroma in physiology. In cancer, however, tissue invasion is driven by the stroma. Myofibroblasts and cancer-associated fibroblasts are important components of the tumor stroma. The origin of myofibroblasts remains controversial, although fibroblasts and bone marrow-derived precursors are considered to be the main progenitor cells. Myofibroblast reactions also occur in fibrosis. Therefore, we wonder whether nontumorous myofibroblasts have different characteristics and different origins as compared to tumor-associated myofibroblasts. The mutual interaction between cancer cells and myofibroblasts is dependent on multiple invasive growth-promoting factors, through direct cell-cell contacts and paracrine signals. Since fibrosis is a major side effect of radiotherapy, we address the question how the main methods of cancer management, including chemotherapy, hormonotherapy and surgery affect myofibroblasts and by inference the surrogate endpoints invasion and metastasis.

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Section: Characterization and Origin Of A Myofibroblastmentioning

confidence: 99%

Stromal myofibroblasts are drivers of invasive cancer growth

Wever¹,

Demetter²,

Mareel³

et al. 2008

Intl Journal of Cancer

631

601

View full text Add to dashboard Cite

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“…SOX-4 directly regulates expression of the Ezh2 gene that encodes the Polycomb group histone methyltransferase and epigenetically modifies expression of several EMT genes [42], [60]. (6) EMT and tumor escape, EMT allows the conversion of tumor cells toward an invasive mesenchymal phenotype allowing (7) intravasation into the circulatory system and (8) CTC chemotactic migration to the lung through the CXCR4/SDF1 axis [71], [72], [73], (9) invasion (extravasation), once in the lung the cells invade the lung tissue at the metastatic niche expressing Extra-cellular Matrix (ECM) degrading matrix metalloproteinase 9 and urokinase plasminogen activator completing the process of [74], [75], [76] (10) metastasis by successful colonization and formation of metastases.…”

Section: Discussionmentioning

confidence: 99%

Core Needle Biopsy of Breast Cancer Tumors Increases Distant Metastases in a Mouse Model

et al. 2014

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INTRODUCTION: Incisional biopsies, including the diagnostic core needle biopsy (CNB), routinely performed before surgical excision of breast cancer tumors are hypothesized to increase the risk of metastatic disease. In this study, we experimentally determined whether CNB of breast cancer tumors results in increased distant metastases and examine important resultant changes in the primary tumor and tumor microenvironment associated with this outcome. METHOD: To evaluate the effect of CNB on metastasis development, we implanted murine mammary 4T1 tumor cells in BALB/c mice and performed CNB on palpable tumors in half the mice. Subsequently, emulating the human scenario, all mice underwent complete tumor excision and were allowed to recover, with attendant metastasis development. Tumor growth, lung metastasis, circulating tumor cell (CTC) levels, variation in gene expression, composition of the tumor microenvironment, and changes in immunologic markers were compared in biopsied and non-biopsied mice. RESULTS: Mice with biopsied tumors developed significantly more lung metastases compared to non-biopsied mice. Tumors from biopsied mice contained a higher frequency of myeloid-derived suppressor cells (MDSCs) accompanied by reduced CD4 + T cells, CD8 + T cells, and macrophages, suggesting biopsy-mediated development of an increasingly immunosuppressive tumor microenvironment. We also observed a CNB-dependent up-regulation in the expression of SOX4, Ezh2, and other key epithelial-mesenchymal transition (EMT) genes, as well as increased CTC levels among the biopsy group. CONCLUSION: CNB creates an immunosuppressive tumor microenvironment, increases EMT, and facilitates release of CTCs, all of which likely contribute to the observed increase in development of distant metastases.

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“…ELISA measurements using the smaller tissue specimens correctly classified risk in 95% of the patients surveyed; however, correlation between individual uPA and PAI-1 levels in the small biopsy specimens versus the larger tissue samples was only 0.789 and 0.901, respectively. Both uPA and PAI-1 are involved in normal tissue-remodeling; consequently, pre-operative diagnostic core needle biopsies can alter their levels 39. It has recently been demonstrated that core biopsies lead to a fibroblastic inflammatory response that results in increased uPA and PAI-1 levels that can persist for up to 9 days in the surrounding tissue and even longer in the area immediately adjacent to the biopsy channel.…”

Section: Introductionmentioning

confidence: 99%

An Ultra-Sensitive Immunoassay for Quantifying Biomarkers in Breast Tumor Tissue

2014

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Urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) have been validated at the highest level of evidence as clinical biomarkers of prognosis in breast cancer. The American Society of Clinical Oncology recommends using uPA and PAI-1 levels in breast tumors for deciding whether patients with newly diagnosed node-negative breast cancer can forgo adjuvant chemotherapy. The sole validated method for quantifying uPA and PAI-1 levels in breast tumor tissue is a colorimetric ELISA assay that takes 3 days to complete and requires 100-300 mg of fresh or frozen tissue. In this study we describe a new assay method for quantifying PAI-1 levels in human breast tumor tissue. This assay combines pressure-cycling technology to extract PAI-1 from breast tumor tissue with a highly sensitive liposome polymerase chain reaction immunoassay for quantification of PAI-1 in the tissue extract. The new PAI-1 assay method reduced the total assay time to one day and improved assay sensitivity and dynamic range by >100, compared to ELISA.

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Influence of preoperative core biopsies on uPA/PAI-1 expression in breast cancer tissue

Cited by 15 publications

References 15 publications

Stromal myofibroblasts are drivers of invasive cancer growth

Stromal myofibroblasts are drivers of invasive cancer growth

Core Needle Biopsy of Breast Cancer Tumors Increases Distant Metastases in a Mouse Model

An Ultra-Sensitive Immunoassay for Quantifying Biomarkers in Breast Tumor Tissue

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