Stromal-Epithelial Interactions During Mammary Gland Development PDF Download
Are you looking for read ebook online? Search for your book and save it on your Kindle device, PC, phones or tablets. Download Stromal-Epithelial Interactions During Mammary Gland Development PDF full book. Access full book title Stromal-Epithelial Interactions During Mammary Gland Development by Malgorzata Gajewska. Download full books in PDF and EPUB format.
Author: Malgorzata Gajewska
Publisher:
ISBN:
Category : Electronic books
Languages : en
Pages : 0
Get Book Here
Book Description
Mammary gland is an organ, which undergoes the majority of its development in the postnatal life of mammals. The complex structure of the mammary gland comprises epithelial and myoepithelial cells forming the parenchymal tissue and adipocytes, fibroblasts, vascular endothelial cells, and infiltrating immune cell composing the stromal compartment. During puberty and in adulthood, circulating hormones released from the pituitary and ovaries regulate the rate of development and functional differentiation of the mammary epithelium. In addition, growing body of evidence shows that interactions between the stromal and parenchymal compartments of the mammary gland play a crucial role in mammogenesis. This regulation takes place on a paracrine level, by locally synthesized growth factors, adipokines, and cytokines, as well as via direct cell-cell interactions. This chapter summarizes the current knowledge about the complex nature of interactions between the mammary epithelium and stroma during mammary gland development in different mammalian species.
Author: Malgorzata Gajewska
Publisher:
ISBN:
Category : Electronic books
Languages : en
Pages : 0
Get Book Here
Book Description
Mammary gland is an organ, which undergoes the majority of its development in the postnatal life of mammals. The complex structure of the mammary gland comprises epithelial and myoepithelial cells forming the parenchymal tissue and adipocytes, fibroblasts, vascular endothelial cells, and infiltrating immune cell composing the stromal compartment. During puberty and in adulthood, circulating hormones released from the pituitary and ovaries regulate the rate of development and functional differentiation of the mammary epithelium. In addition, growing body of evidence shows that interactions between the stromal and parenchymal compartments of the mammary gland play a crucial role in mammogenesis. This regulation takes place on a paracrine level, by locally synthesized growth factors, adipokines, and cytokines, as well as via direct cell-cell interactions. This chapter summarizes the current knowledge about the complex nature of interactions between the mammary epithelium and stroma during mammary gland development in different mammalian species.
Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 42
Get Book Here
Book Description
The purpose of this grant is to define interactions between stroma and epithelium in mammary oncogenesis in mice transgenic for Shope growth factor (SGF). Different lines of SGF transgenic mice express this EGF-like cytokine using inducible (metallothionein, MT) or constitutive (RSV-LTR) promoters. For the year now ending, most stated goals have been met, although some remain. We made sufficient SGF-transgenic mice of RSV-SGF and MT-SGF lines to analyze mammary differentiation and oncogenesis, including testing SGF expression and that of particular cellular genes that are important in these processes. It also induced defining which cells express the transgene and these cellular genes. We have also interbred RSV- and MT-SGF transgenic mice with p53-/- mice, to determine the nature of the interactions between homozygous deletion of p53 tumor suppressor gene and SGF expression as regards mammary gland development and tumorigenesis. These mice have been analyzed, and additional numbers of them are being produced. Our study of SGF activity in cultured cells has been progressing more slowly, and these studies are largely still in progress. Thus, our studies of the effects of SGF on the murine mammary gland are proceeding, and additional work is in progress.
Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
Get Book Here
Book Description
We identified molecules that are involved in the cross talk between the epithelial and mesenchymal components of the developing and involuting mammary gland. The EFGR protein was shown to mediate normal ductal morphogenesis by acting from the stromal cells on the development of the mammary epithelial ducts. Additional evidence was provided concerning the function of the Caspase 1 gene product during lobular-alveolar development and involution of the mammary gland after weaning. An interesting observation from this work was mammary epithelial cells that will succumb to apoptosis enter the cell cycle first. This observation implies that at least a subset of the redundant epithelial cells undergo activation before cell death. In preliminary work mammary glands from the MMP14 null mouse were shown to have less adipose tissue but ductal penetration of the fat pad and initial duct formation occurred by post-natal day 13. Further experimentation is required to determine if the reduction in adipose tissue is related - to the wasting phenotype of these animals, or is induced by the MMP14 null epithelial cells. The practical outcome of these studies is a better understanding of mammary gland development before, during and after pregnancy, and during the process of involution.
Author: Shiqing Wang
Publisher:
ISBN:
Category : Estrogen
Languages : en
Pages : 268
Get Book Here
Book Description
Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
Get Book Here
Book Description
Recent studies from our laboratory have demonstrated that parathyroid hormone related protein (PTHrP) is necessary for mammary gland development. Our studies have suggested that PTHrP is involved in regulating epithelial-stromal interactions during embryonic mammary development and during adolescent ductal morphogenesis. It is our working hypothesis that PTHrP is an epithelial signal that acts to modulate the ability of mammary stromal cells to support epithelial morphogenesis. In the second year of this project, we have gathered additional evidence that PTHrP plays a critical role in the control of mammary stromal cell function. We have shown that PTHrP is the signal from the mammary epithelium that necessary for the proper differentiation of the mammary mesenchyme. In addition, we have also shown that mammary stromal cells must express the PPRl in order to support mammary epithelial morphogenesis, thereby conclusively demonstrating that stromal cells are the critical target for PTHrP's actions in the mammary gland. Finally, we have begun to identify potential downstream signaling partners to PTHrP in mammary stromal cells in order to elucidate the mechanisms by which PTHrP modulates stromal cell function.
Author: Bryony Wiseman
Publisher:
ISBN:
Category :
Languages : en
Pages : 18
Get Book Here
Book Description
The mammary gland relies on stromal-epithelial interactions for proper development. Tumorigenesis occurs when these signals are misinterpreted. Here we show that stromal matrix metalloproteinases (MMPs) have distinct roles in mammary gland branching morphogenesis. MMP activity is required for normal mammary gland development since mice treated with a synthetic MMP inhibitor, GM6OOl, have retarded ductal development. Furthermore, 3D cultures of mammary organoids also require MMP activity to branch in response to growth factors, indicating a mammary specific response. We also show that specific MMPs are required for distinct aspects of mammary gland morphogenesis. Specifically, MMF-3 is needed for branching because MMP-3 null mice have significantly fewer branches than controls. However, the ductal length is normal. In contrast, MMP-2 is required for ductal elongation, since the ducts of MMP-2 null mice are retarded in their penetration into the fat pad. However, the branching of the MMP-2 null ducts is normal. MMP-l4 is a known activator of MMP-2 and we show it is highly expressed in front of terminal end buds. Mammary glands deficient in MMP-l4 grown under the kidney capsule of nude mice also have defective ductal morphogenesis. Thus, these stromal enzymes are important, and have distinct roles, in patterning the mammary gland.
Author: Mani T. Valarmathi
Publisher: BoD – Books on Demand
ISBN: 1789849845
Category : Science
Languages : en
Pages : 262
Get Book Here
Book Description
Stromal cells are connective tissue cells of any organ, and they support the function of the parenchymal cells of that particular organ. Stromal/stromal stem cells are fundamentally a heterogeneous population of cells with contradictory differentiation potential depending upon their environmental niche. Stromal cell biology is not only intriguing, but equally stromal cell ontogeny in vivo remains challenging. In recent years there has been substantial advances in our understanding of stromal cell biology, especially stromal cell isolation, characterization, differentiation, and interactions in physiological (epithelial-stromal interactions) as well as pathophysiological (stromal-cancer interactions) contexts. In addition, stromal cells are also utilized more and more as a therapeutic tool not only in the field of gene therapy but also in the translational field of tissue engineering and regenerative medicine. Therefore, the goal of this book is to consolidate the recent advances in the area of stromal/stromal stem cell biology covering a broad range of interrelated topics in a timely fashion and to disseminate that knowledge in a lucid way to a greater scientific audience. This book will prove highly useful for students, researchers, and clinicians in stem cell biology, developmental biology, cancer biology, pathology, oncology, as well as tissue engineering and regenerative medicine. This quick reference will benefit anyone desiring a thorough overview of stromal cell structure, function, and its therapeutic implications.
Author: Young Chul Kim
Publisher:
ISBN:
Category :
Languages : en
Pages : 154
Get Book Here
Book Description
Author:
Publisher:
ISBN:
Category :
Languages : en
Pages :
Get Book Here
Book Description
Extracellular matrix and extracellular matrix-degrading matrix metalloproteinases play a key role in interactions between the epithelium and the mesenchyme during mammary gland development and disease. In patients with breast cancer, the mammary mesenchyme undergoes a stromal reaction, the etiology of which is unknown. We previously showed that targeting of an autoactivating mutant of the matrix metalloproteinase stromelysin-1 to mammary epithelia of transgenic mice resulted in reduced mammary function during pregnancy and development of preneoplastic and neoplastic lesions. Here we examine the cascade of alterations before breast tumor formation in the mammary gland stroma once the expression of the stromelysin-1 transgene commences. Beginning in postpubertal virgin animals, low levels of transgene expression in mammary epithelia led to increased expression of endogenous stromelysin-1 in stromal fibroblasts and up-regulation of other matrix metalloproteinases, without basement membrane disruption. These changes were accompanied by the progressive development of a compensatory reactive stroma, characterized by increased collagen content and vascularization in glands from virgin mice. This remodeling of the gland affected epithelial-mesenchymal communication as indicated by inappropriate expression of tenascin-C starting by day 6 of pregnancy. This, together with increased transgene expression, led to basement membrane disruption starting by day 15 of pregnancy. We propose that the highly reactive stroma provides a prelude to breast epithelial tumors observed in these animals. Epithelial development depends on an exquisite series of inductive and instructive interactions between the differentiating epithelium and the mesenchymal (stromal) compartment. The epithelium, which consists of luminal and myoepithelial cells, is separated from the stroma by a basement membrane (BM), which plays a central role in mammary gland homeostasis and gene expression. In vivo, stromal cells produce fibronectin, collagens, proteoglycans, and some components of the BM, as well as a number of proteinases that can effectively degrade BM constituents. Stromal and epithelial cells of the mammary gland interact to regulate BM synthesis and degradation and, thus, mammary function. Matrix metalloproteinases (MMPs) are extracellular matrix (ECM)-degrading enzymes involved in mammary gland morphogenesis and involution. During late pregnancy and lactation, when the gland becomes fully functional, the expression of MMPs is low however, during involution, when the gland loses function and is remodeled, synthesis of ECM-degrading proteinases increases dramatically. 11 Disturbance of the balance between MMPs and MMP inhibitors leads to either unscheduled involution or prolonged lactation. Mammary glands of virgin mice expressing an autoactivating stromelysin-1 (SL-1) transgene display supernumerary branches and precocious alveolar development, accompanied by the synthesis of [beta]-casein at levels found normally only during early pregnancy. During late pregnancy, increased expression of the SL-1 transgene leads to a reduction in expression of pregnancy-specific genes. Later in life, some SL-1 transgenic mice develop hyperplastic, dysplastic, and ductal carcinoma in situ-like lesions, as well as malignant tumors. Little is known about the sequence of changes that occurs before formation of an overt reactive stroma in breast cancer. In the present study, we address the question of whether and how the stromal compartment is altered as a consequence of inappropriate SL-1 transgene expression in the epithelium.
Author: Maricel V. Maffini
Publisher:
ISBN:
Category :
Languages : en
Pages : 20
Get Book Here
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.
