Breast Carcinogenesis: Stroma-Epithelium Interactions PDF Download
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Author: Maricel V. Maffini
Publisher:
ISBN:
Category :
Languages : en
Pages : 20
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A complex network of signals between the stroma, the extracellular matrix and the epithelium, and by hormones acting systemically, drive the mammary gland development and function. The tissue organization field theory (TOFT) proposes that alterations of the reciprocal interactions between stroma and epithelium initiate the process of neoplastic transformation of epithelial cells. Our goal is to assess whether the primary target of the carcinogen N-nitroso-methylurea (NMU) is the epithelium, the stroma or both through a protocol of tissue recombination by transplanting mammary gland epithelial cells (MGEC) into mammary gland fat pads (MGFP) previously cleared of epithelium. The animals were divided into 6 groups: (1) NMu-exposed stroma and vehicle (VEH)-exposed MGEC; (2) NMU exposed stroma and NMU-exposed MGEC; (3) VEH-exposed stroma and NMU-exposed MGEC; (4) VEH- exposed stroma and VEH-exposed MGEC; (S) positive control (intact virgin rat exposed to NMU); (6) negative control (exposed to VEH). Results: the tumor incidence was Gl 83.3%, G2 85.7%, 03, 4 and 6 0%, OS 100%. Our results show that the stroma, rather than the epithelial cells, may be responsible for the development of a neoplasia. This novel concept in carcinogenesis will provide clues to be applied to more rational study of breast cancer.
Author: Maricel V. Maffini
Publisher:
ISBN:
Category :
Languages : en
Pages : 20
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Book Description
A complex network of signals between the stroma, the extracellular matrix and the epithelium, and by hormones acting systemically, drive the mammary gland development and function. The tissue organization field theory (TOFT) proposes that alterations of the reciprocal interactions between stroma and epithelium initiate the process of neoplastic transformation of epithelial cells. Our goal is to assess whether the primary target of the carcinogen N-nitroso-methylurea (NMU) is the epithelium, the stroma or both through a protocol of tissue recombination by transplanting mammary gland epithelial cells (MGEC) into mammary gland fat pads (MGFP) previously cleared of epithelium. The animals were divided into 6 groups: (1) NMu-exposed stroma and vehicle (VEH)-exposed MGEC; (2) NMU exposed stroma and NMU-exposed MGEC; (3) VEH-exposed stroma and NMU-exposed MGEC; (4) VEH- exposed stroma and VEH-exposed MGEC; (S) positive control (intact virgin rat exposed to NMU); (6) negative control (exposed to VEH). Results: the tumor incidence was Gl 83.3%, G2 85.7%, 03, 4 and 6 0%, OS 100%. Our results show that the stroma, rather than the epithelial cells, may be responsible for the development of a neoplasia. This novel concept in carcinogenesis will provide clues to be applied to more rational study of breast cancer.
Author: Itzhak D. Goldberg
Publisher: Birkhäuser
ISBN: 3034890702
Category : Science
Languages : en
Pages : 304
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Book Description
The contribution of epithelia-mesenchyme interaction to normal development (eg., tissue formation) and to neoplasia has become a subject of increasing interest to scientists because of recent progress in deciphering the molecular signals that mediate this interaction. Clearly, some of the same types of molecules (eg., growth factors and their receptors, proteolytic enzymes, cell adhesion molecules, and structural proteins of the extracellular matrix) mediate exchange of information between epithelia and mesenchyme during normal development and malignant growth. However, defects in the regulation of this exchange appear to contribute to malignancy by allowing growth promoting, invasogenic, and angiogenic factors to accumulate within the microenvironment of the tumor. For example, recent studies suggest that abnormal interactions between tumor epithelial cells and stromal mesenchymal cells contribute to the overproduction and accumulation of scatter factor (hepatocyte growth factor), an invasogenic and angiogenic cytokine, in certain types of tumor. The production and and activation of type IV collagenase, a matrix-degrading enzyme required for tumor cell invasion, appears to require intimate cooperation between tumor and stromal cells. The material contained in this volume highlights the state-of-the-art of knowledge of the molecular mechanisms by which epithelia and mesenchyme collaborate, and the abnormalities in these mechanisms that may lead to the development of cancer.
Author:
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Category :
Languages : en
Pages : 27
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The work done to date has helped to better characterize the breast cancer microenvironment. We have confirmed that the expression normal adjacent tissue is not distinct from healthy breast reduction tissue. The genes specific to normal epithelium also identify basal-like breast tumors, potentially explaining their resistance to treatment. The interactions involving the tumor immune cells have the strongest detectable signals using the methods developed by this project. We are the first group to characterize the expression of the blood vessels in breast cancer. We have confirmed the presence of low-density mature vessels and high-density immature vessels. Surprisingly, the expression from those mature tumor vessels more closely match the characteristics of tumor vessels in other cancers. This will open new roads for a better understanding of neo-vascularization in breast cancer as well as helping to target treatment more effectively. Our work in mouse models has also identified osteoactivin as a potential effector of bone metastasis.
Author: C. Palmieri
Publisher:
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Category :
Languages : en
Pages :
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Author: Eldo Thomas Verghese
Publisher:
ISBN:
Category :
Languages : en
Pages : 422
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Author: Stephanie Chantal Lebret
Publisher:
ISBN:
Category : Breast
Languages : en
Pages : 472
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This study determined that the microenvironment influences mammary cellular development and that this microenvironment differs between normal and malignant tissue. Cancer-associated fibroblasts, loss of an extracellular protein and presence of a growth factor were demonstrated to influence cancer cell migration, presenting a basis for the understanding of breast cancer metastasis.
Author: Kun-Chih Kelvin Tsai
Publisher:
ISBN:
Category : Breast
Languages : en
Pages : 284
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Author: Alison Sarah Waterworth
Publisher:
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Category :
Languages : en
Pages : 334
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Category :
Languages : en
Pages : 8
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Tumor progression is characterized by altered cell-cell interactions, increased invasion and angiogenesis, and upregulation of integrins including alpha5 and av; as well as increased tenascin (TN) and fibronectin (FN) deposition. We asked whether elevated alpha5 integrin could promote malignant progression by compromising tissue polarity and promoting angiogenesis. Using the HMT3522 breast cancer progression cell series and 3D reconstituted basement membrane (rBM) co-culture and xenograft assays we found that malignant transformation correlated with loss of tissue polarity, acquisition of invasiveness, increased alpha5 integrin expression, VEGF and IL-8 upregulation, and a pro-angiogenic phenotype in culture and in vivo. However, only inhibiting alpha5beta1 activity could phenotypically revert these tumors, reduce invasion and impair angiogenesis in culture and in vivo. Moreover, overexpression of alpha5 integrin in S-l nonmalignant cells compromised polarity and induced angiogenesis in vitro and in vivo. Thus, we propose that alpha5beta1 integrin ligation of FN - regulates tissue architecture- mediated (TAM)-dormancy through cooperative interaction and induction or angiogenesis.
Author: Sanober Aftab Amin
Publisher:
ISBN:
Category :
Languages : en
Pages : 338
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