Browsing by Subject "Tumor stroma"

Now showing 1 - 3 of 3
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    Microenvironment in breast tumorigenesis: Friend or foe?
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Martins, Diana; Schmitt, Fernando
    It is now widely accepted that the tumor microenvironment is a pathologically active niche that shapes tumor nature, evolution and response to treatment. Close interactions between cancer cells and stroma are known to regulate several cancer pathways and thus the determination of different tumor-stromal interactions could be an important step in invasiveness. The breast cancer microenvironment is a complex combination of several different cell types and molecules and a key contributor to tumor development and progression. The microenvironment includes fibroblasts, macrophages, immune cells, tumor-infiltrating lymphocytes, endothelial cells and angiogenic vascular cells, whereas stromal cells surround and interact with tumor cells. Recent data demonstrate significant gene expression alterations in microenvironment cells during disease progression and several stromal cell types are implicated in promoting the “hallmarks of cancer”, which can be explored as targets for cancer therapy. Besides identifying new therapeutic targets, the microenvironment has also been implicated in chemotherapy resistance, suggesting that the crosstalk between cancer and its microenvironment is a promising strategy to target breast cancer.
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    The role of proteoglycans in the reactive stroma on tumor growth and progression
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Coulson-Thomas, Yvette May; Gesteira Ferreira, Tarsis; Lawrence Norton, Andrew; W-Y Kao, Winston; Bonciani Nader, Helena; Coulson-Thomas, Vivien Jane
    The stroma surrounding tumors can either restrict or promote tumor growth and progression, and both the cellular and non-cellular components of the stroma play an active role. The cellular components in the surrounding stroma include tumor-associated fibroblasts, host tissue cells and immune cells. The noncellular components, which form the extracellular matrix (ECM) scaffold, include proteoglycans, collagen, proteinases, growth factors and cytokines. For tumorigenesis to occur it is necessary for tumor cells to modify the surrounding stroma. Tumor cells have mechanisms for achieving this, such as co-opting fibroblasts and modifying the ECM they produce, degrading the surrounding ECM and/or synthesizing a favorable ECM to support invasion. Proteoglycans are an important component of the ECM and play an active role in tumor growth and progression. The expression and glycosylation patterns of proteoglycans are altered in the stroma surrounding tumors and these molecules may support or restrict tumor growth and progression depending on the type and stage of tumor. In the present review we discuss the difference between the tumor promoting and restricting stromal reactions surrounding tumors and the role proteoglycans play.
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    Tumor stroma is the predominant uPA-, uPAR-, PAI-1-expressing tissue in human breast cancer: prognostic impact
    (Murcia : F. Hernández, 2009) Hildenbrand, Ralf; Schaaf, Antonela; Dorn-Beineke, Alexandra; Allgayer, Heike; Sütterlin, Marc; Marx, Alexander; Stroebel, Philipp
    Urokinase-type plasminogen activator (uPA), its receptor (uPAR) and its inhibitor PAI-1, play a key role in tumor invasion and metastasis. uPA and PAI-1 were the first novel tumor biological factors to be validated at the highest level of evidence regarding their clinical utility in breast cancer. Their antigens are determined in tumor tissue extracts by standardized, quality-assured immunometric assays (ELISA). Since the late 1980s, numerous independent studies have demonstrated that patients with low levels of uPA- and PAI-1 in their primary tumor tissue have significantly better survival than patients with high levels of either factor. However, it is unclear whether it is their (relative) levels in the tumor stroma or in the tumor cells themselves that is most relevant to patient outcome. This missing knowledge leads to an uncertainty concerning the management of breast cancer tissue specimens. It is unclear how much tumor stroma is allowed in one tumor tissue specimen for an adequate assessment of the patients' outcome. This is the first study in which tumor cells and stromal tissue of invasive breast carcinomas (n=60) were separated by laser capture microdissection followed by ELISA-based determination of the uPA-, uPAR- and PAI-1-levels. In addition, we have assessed uPA-, uPAR- and PAI-1 distribution in formalin-fixed, paraffin-embedded breast cancer specimens (n=60) by immunohistochemistry. The uPA-, uPAR- and PAI-1 in tumor stroma only, tumor cells only and not separated tumor tissue did not show any significant differences in protein-levels determined by ELISA. Cox regression analysis showed that patients with high uPA-, high uPAR-, and/or high PAI-1-levels, as compared to patients with low levels of either factor, showed a significantly shorter relapse-free survival and overall survival (p=0.000001). These results suggest that a strong expression of uPA, uPAR and PAI-1 in the tumor stroma, as well as in tumor cells, have the same impact on the clinical behaviour of breast cancer. Conclusion: When using uPA- and PAI-1 levels as prognostic and predictive factors in breast cancer the quantity of tumor stroma in the tumor tissue specimen is not relevant for the assessment of the patients' outcome.