共查询到20条相似文献,搜索用时 46 毫秒
1.
Josephine A. Wright Jennifer K. Richer Gregory J. Goodall 《Journal of mammary gland biology and neoplasia》2010,15(2):213-223
MicroRNAs are master regulators of gene expression in many biological and pathological processes, including mammary gland
development and breast cancer. The differentiation program termed the epithelial to mesenchymal transition (EMT) involves
changes in a number of microRNAs. Some of these microRNAs have been shown to control cellular plasticity through the suppression
of EMT-inducers or to influence cellular phenotype through the suppression of genes involved in defining the epithelial and
mesenchymal cell states. This has led to the suggestion that microRNAs maybe a novel therapeutic target for the treatment
of breast cancer. In this review, we will discuss microRNAs that are involved in EMT in mammary cells and breast cancer. 相似文献
2.
Douglas S. Micalizzi Susan M. Farabaugh Heide L. Ford 《Journal of mammary gland biology and neoplasia》2010,15(2):117-134
From the earliest stages of embryonic development, cells of epithelial and mesenchymal origin contribute to the structure
and function of developing organs. However, these phenotypes are not always permanent, and instead, under the appropriate
conditions, epithelial and mesenchymal cells convert between these two phenotypes. These processes, termed Epithelial-Mesenchymal
Transition (EMT), or the reverse Mesenchymal-Epithelial Transition (MET), are required for complex body patterning and morphogenesis.
In addition, epithelial plasticity and the acquisition of invasive properties without the full commitment to a mesenchymal
phenotype are critical in development, particularly during branching morphogenesis in the mammary gland. Recent work in cancer
has identified an analogous plasticity of cellular phenotypes whereby epithelial cancer cells acquire mesenchymal features
that permit escape from the primary tumor. Because local invasion is thought to be a necessary first step in metastatic dissemination,
EMT and epithelial plasticity are hypothesized to contribute to tumor progression. Similarities between developmental and
oncogenic EMT have led to the identification of common contributing pathways, suggesting that the reactivation of developmental
pathways in breast and other cancers contributes to tumor progression. For example, developmental EMT regulators including
Snail/Slug, Twist, Six1, and Cripto, along with developmental signaling pathways including TGF-β and Wnt/β-catenin, are misexpressed
in breast cancer and correlate with poor clinical outcomes. This review focuses on the parallels between epithelial plasticity/EMT
in the mammary gland and other organs during development, and on a selection of developmental EMT regulators that are misexpressed
specifically during breast cancer. 相似文献
3.
Evette S. Radisky Derek C. Radisky 《Journal of mammary gland biology and neoplasia》2010,15(2):201-212
Matrix metalloproteinases (MMPs) degrade and modify the extracellular matrix (ECM) as well as cell-ECM and cell-cell contacts, facilitating detachment of epithelial cells from the surrounding tissue. MMPs play key functions in embryonic development and mammary gland branching morphogenesis, but they are also upregulated in breast cancer, where they stimulate tumorigenesis, cancer cell invasion and metastasis. MMPs have been investigated as potential targets for cancer therapy, but clinical trials using broad-spectrum MMP inhibitors yielded disappointing results, due in part to lack of specificity toward individual MMPs and specific stages of tumor development. Epithelial-mesenchymal transition (EMT) is a developmental process in which epithelial cells take on the characteristics of invasive mesenchymal cells, and activation of EMT has been implicated in tumor progression. Recent findings have implicated MMPs as promoters and mediators of developmental and pathogenic EMT processes in the breast. In this review, we will summarize recent studies showing how MMPs activate EMT in mammary gland development and in breast cancer, and how MMPs mediate breast cancer cell motility, invasion, and EMT-driven breast cancer progression. We also suggest approaches to inhibit these MMP-mediated malignant processes for therapeutic benefit. 相似文献
4.
The Epithelial-to-Mesenchymal Transition and Cancer Stem Cells: A Coalition Against Cancer Therapies
Brett G. Hollier Kurt Evans Sendurai A. Mani 《Journal of mammary gland biology and neoplasia》2009,14(1):29-43
During cancer progression, some cells within the primary tumor may reactivate a latent embryonic program known as epithelial-to-mesenchymal
transition (EMT). Through EMT, transformed epithelial cells can acquire the mesenchymal traits that seem to facilitate metastasis.
Indeed, there is accumulating evidence that EMT and mesenchymal-related gene expression are associated with aggressive breast
cancer subtypes and poor clinical outcome in breast cancer patients. More recently, the EMT program was shown to endow normal
and transformed mammary epithelial cells with stem cell properties, including the ability to self-renew and efficiently initiate
tumors. This link between EMT and stem cells may have numerous implications in the progression of breast tumors. The EMT process
may facilitate the generation of cancer cells with the mesenchymal traits needed for dissemination as well as the self-renewal
properties needed for initiation of secondary tumors. Breast cancer stem cells are resistant to many conventional cancer therapies,
which can promote tumor relapse. Therefore, the generation of cancer stem cells by EMT may promote the development of refractory
and resistant breast tumors. The purpose of this review is to summarize the findings related to EMT and stem cells in cancer
progression and therapy resistance. 相似文献
5.
Carcinogenesis is a complex process during which cells undergo genetic and epigenetic alterations. These changes can lead
tumor cells to acquire characteristics that enable movement from the primary site of origin when conditions become unfavorable.
Such characteristics include gain of front-rear polarity, increased migration/invasion, and resistance to anoikis, which facilitate
tumor survival during metastasis. An epithelial to mesenchymal transition (EMT) constitutes one way that cancer cells can
gain traits that promote tumor progression and metastasis. Two microRNA (miRNA) families, the miR-200 and miR-221 families,
play crucial opposing roles that affect the differentiation state of breast cancers. These two families are differentially
expressed between the luminal A subtype of breast cancer as compared to the less well-differentiated triple negative breast
cancers (TNBCs) that exhibit markers indicative of an EMT. The miR-200 family promotes a well-differentiated epithelial phenotype,
while high miR-221/222 results in a poorly differentiated, mesenchymal-like phenotype. This review focuses on the mechanisms
(specific proven targets) by which these two miRNA families exert opposing effects on cellular plasticity during breast tumorigenesis
and metastasis. 相似文献
6.
Katharine M. Hardy Brian W. Booth Mary J. C. Hendrix David S. Salomon Luigi Strizzi 《Journal of mammary gland biology and neoplasia》2010,15(2):191-199
Activation of the ErbB family of receptor tyrosine kinases via cognate Epidermal Growth Factor (EGF)-like peptide ligands
constitutes a major group of related signaling pathways that control proliferation, survival, angiogenesis and metastasis
of breast cancer. In this respect, clinical trials with various ErbB receptor blocking antibodies and specific tyrosine kinase
inhibitors have proven to be partially efficacious in the treatment of this heterogeneous disease. Induction of an embryonic
program of epithelial-to-mesenchymal transition (EMT) in breast cancer, whereupon epithelial tumor cells convert to a more
mesenchymal-like phenotype, facilitates the migration, intravasation, and extravasation of tumor cells during metastasis.
Breast cancers which exhibit properties of EMT are highly aggressive and resistant to therapy. Activation of ErbB signaling
can regulate EMT-associated invasion and migration in normal and malignant mammary epithelial cells, as well as modulating
discrete stages of mammary gland development. The purpose of this review is to summarize current information regarding the
role of ErbB signaling in aspects of EMT that influence epithelial cell plasticity during mammary gland development and tumorigenesis.
How this information may contribute to the improvement of therapeutic approaches in breast cancer will also be addressed. 相似文献
7.
8.
Xu J Wang R Xie ZH Odero-Marah V Pathak S Multani A Chung LW Zhau HE 《The Prostate》2006,66(15):1664-1673
BACKGROUND: The ARCaP cell line was established from the ascites fluid of a patient with metastatic prostate cancer. This study characterized the host microenvironmental role in cancer progression, epithelial to mesenchymal transition (EMT), and bone and adrenal metastasis in parental ARCaP and its derived cell subclones. METHODS: Cytogenetic profiles, growth, migration, invasion, cellular interaction, drug sensitivities, and gene expression of ARCaP cell subclones were compared. In vivo gene expression, behavior, and metastasis of ARCaP subclones were analyzed by serial intracardiac injections into SCID mice. RESULTS: ARCaP(E) cells, with cobblestone morphology, underwent EMT through cellular interaction with host bone and adrenal gland. Lineage-derived ARCaP(M) cells, with spindle-shape fibroblastic morphology, exhibited decreased cell adhesion and increased metastasis to bone and adrenal gland. Cytogenetic analyses of parental and ARCaP subclones confirmed their clonality. CONCLUSIONS: ARCaP uniquely models the molecular basis of prostate cancer bone and adrenal metastases and epithelial to mesenchymal transition. 相似文献
9.
Mammary myoepithelial cells have been a neglected facet of breast cancer biology, largely ignored since they have been considered
to be less important for tumorigenesis than luminal epithelial cells from which most of breast carcinomas are thought to arise.
In recent years as our knowledge of stem cell biology and the cellular microenvironment has been increasing, myoepithelial
cells are slowly starting to gain more attention. Emerging data raise the hypothesis whether myoepithelial cells play a key
role in breast tumor progression by regulating the in situ to invasive carcinoma transition and that myoepithelial cells are part of the mammary stem cell niche. Paracrine interactions
between myoepithelial and luminal epithelial cells are known to be important for regulation of cell cycle progression, establishing
epithelial cell polarity, and inhibiting cell migration and invasion. Based on these functions, normal mammary myoepithelial
cells have been called
“natural tumor suppressors.” However, during tumor progression myoepithelial cells seem to loose these properties, and eventually
this cell population diminishes as tumors become invasive. Better understanding of myoepithelial cell function and their role
in tumor progression may lead to their exploitation for cancer therapeutic and preventative measures. 相似文献
10.
11.
Parvani JG Taylor MA Schiemann WP 《Journal of mammary gland biology and neoplasia》2011,16(2):127-146
Breast cancer is a heterogeneous disease comprised of at least five major tumor subtypes that coalesce as the second leading
cause of cancer death in women in the United States. Although metastasis clearly represents the most lethal characteristic
of breast cancer, our understanding of the molecular mechanisms that govern this event remains inadequate. Clinically, ~30%
of breast cancer patients diagnosed with early-stage disease undergo metastatic progression, an event that (a) severely limits treatment options, (b) typically results in chemoresistance and low response rates, and (c) greatly contributes to aggressive relapses and dismal survival rates. Transforming growth factor-β (TGF-β) is a pleiotropic
cytokine that regulates all phases of postnatal mammary gland development, including branching morphogenesis, lactation, and
involution. TGF-β also plays a prominent role in suppressing mammary tumorigenesis by preventing mammary epithelial cell (MEC)
proliferation, or by inducing MEC apoptosis. Genetic and epigenetic events that transpire during mammary tumorigenesis conspire
to circumvent the tumor suppressing activities of TGF-β, thereby permitting late-stage breast cancer cells to acquire invasive
and metastatic phenotypes in response to TGF-β. Metastatic progression stimulated by TGF-β also relies on its ability to induce
epithelial-mesenchymal transition (EMT) and the expansion of chemoresistant breast cancer stem cells. Precisely how this metamorphosis
in TGF-β function comes about remains incompletely understood; however, recent findings indicate that the initiation of oncogenic
TGF-β activity is contingent upon imbalances between its canonical and noncanonical signaling systems. Here we review the
molecular and cellular contributions of noncanonical TGF-β effectors to mammary tumorigenesis and metastatic progression. 相似文献
12.
Molly A. Taylor Jenny G. Parvani William P. Schiemann 《Journal of mammary gland biology and neoplasia》2010,15(2):169-190
Epithelial-mesenchymal transition (EMT) is an essential process that drives polarized, immotile mammary epithelial cells (MECs)
to acquire apolar, highly migratory fibroblastoid-like features. EMT is an indispensable process that is associated with normal
tissue development and organogenesis, as well as with tissue remodeling and wound healing. In stark contrast, inappropriate
reactivation of EMT readily contributes to the development of a variety of human pathologies, particularly those associated
with tissue fibrosis and cancer cell invasion and metastasis, including that by breast cancer cells. Although metastasis is
unequivocally the most lethal aspect of breast cancer and the most prominent feature associated with disease recurrence, the
molecular mechanisms whereby EMT mediates the initiation and resolution of breast cancer metastasis remains poorly understood.
Transforming growth factor-β (TGF-β) is a multifunctional cytokine that is intimately involved in regulating numerous physiological
processes, including cellular differentiation, homeostasis, and EMT. In addition, TGF-β also functions as a powerful tumor
suppressor in MECs, whose neoplastic development ultimately converts TGF-β into an oncogenic cytokine in aggressive late-stage
mammary tumors. Recent findings have implicated the process of EMT in mediating the functional conversion of TGF-β during
breast cancer progression, suggesting that the chemotherapeutic targeting of EMT induced by TGF-β may offer new inroads in
ameliorating metastatic disease in breast cancer patients. Here we review the molecular, cellular, and microenvironmental
factors that contribute to the pathophysiological activities of TGF-β during its regulation of EMT in normal and malignant
MECs. 相似文献
13.
14.
The Organization of Tight Junctions in Epithelia: Implications for Mammary Gland Biology and Breast Tumorigenesis 总被引:4,自引:0,他引:4
Tight junctions (TJs), the most apical components of the cell-cell junctional complexes, play a crucial role in the establishment and maintenance of cell polarity within tissues. In secretory glandular tissues, such as the mammary gland, TJs are crucial for separating apical and basolateral domains. TJs also create the variable barrier regulating paracellular movement of molecules through epithelial sheets, thereby maintaining tissue homeostasis. Recent advances reveal that TJs exist as macromolecular complexes comprised of several types of membrane proteins, cytoskeletal proteins, and signaling molecules. Many of these components are regulated during mammary gland development and pregnancy cycles, and several have received much attention as possible "tumor suppressors" during progression to breast cancer. 相似文献
15.
Hector R. Contreras Rodrigo A. Ledezma Jorge Vergara Federico Cifuentes Cristina Barra Pablo Cabello Ivan Gallegos Bernardo Morales Christian Huidobro Enrique A. Castellón 《Urologic oncology》2010,28(5):534-540
The epithelial-mesenchymal transition (EMT) is considered a key step in tumor progression, where the invasive cancer cells change from epithelial to mesenchymal phenotype. During this process, a decrease or loss in adhesion molecules expression and an increase in migration molecules expression are observed. The aim of this work was to determine the expression and cellular distribution of syndecan-1 and -2 (migration molecules) and E-cadherin and β-catenin (adhesion molecules) in different stages of prostate cancer progression. A quantitative immunohistochemical study of these molecules was carried out in tissue samples from benign prostatic hyperplasia and prostate carcinoma, with low and high Gleason score, obtained from biopsies archives of the Clinic Hospital of the University of Chile and Dipreca Hospital. Polyclonal specific antibodies and amplification system of estreptavidin-biotin peroxidase and diaminobenzidine were used. Syndecan-1 was uniformly expressed in basolateral membranes of normal epithelium, changing to a granular cytoplasmatic expression pattern in carcinomas. Syndecan-2 was observed mainly in a cytoplasmatic granular pattern, with high immunostaining intensity in areas of low Gleason score. E-cadherin was detected in basolateral membrane of normal epithelia showing decreased expression in high Gleason score samples. β-Catenin was found in cell membranes of normal epithelia changing its distribution toward the nucleus and cytoplasm in carcinoma samples. We concluded that changes in expression and cell distribution of E-cadherin and β-catenin correlated with the progression degree of prostate adenocarcinoma, suggesting a role of these molecules as markers of progression and prognosis. Furthermore, changes in the pattern expression of syndecan-1 and -2 indicate that both molecules may be involved in the EMT and tumor progression of prostate cancer. 相似文献
16.
Camila Leonel Thaiz Ferraz Borin Lívia de Carvalho Ferreira Marina Gobbe Moschetta Marcio Chaim Bajgelman Alicia M. Viloria-Petit Debora Aparecida Pires de Campos Zuccari 《Journal of mammary gland biology and neoplasia》2017,22(1):27-41
Epithelial mesenchymal transition (EMT) is a process by which epithelial cells acquire mesenchymal properties, generating metastases. Transforming growth factor beta (TGF-β) is associated with this malignancy by having the ability to induce EMT. Metformin, has been shown to inhibit EMT in breast cancer cells. Based on this evidence we hypothesize that treatment with metformin and the silencing of TGF-β, inhibits the EMT in cancer cells. Canine metastatic mammary tumor cell line CF41 was stably transduced with a shRNA-lentivirus, reducing expression level of TGF-β1. This was combined with metformin treatment, to look at effects on cell migration and the expression of EMT markers. For in vivo study, unmodified or TGF-β1sh cells were injected in the inguinal region of nude athymic female mice followed by metformin treatment. The mice’s lungs were collected and metastatic nodules were subsequently assessed for EMT markers expression. The migration rate was lower in TGF-β1sh cells and when combined with metformin treatment. Metformin treatment reduced N-cadherin and increased E-cadherin expression in both CF41 and TGF-β1sh cells. Was demonstrated that metformin treatment reduced the number of lung metastases in animals bearing TGF-β1sh tumors. This paralleled a decreased N-cadherin and vimentin expression, and increased E-cadherin and claudin-7 expression in lung metastases. This study confirms the benefits of TGF-β1 silencing in addition to metformin as potential therapeutic agents for breast cancer patients, by blocking EMT process. To the best of our knowledge, we are the first to report metformin treatment in cells with TGF-β1 silencing and their effect on EMT. 相似文献
17.
Fridriksdottir AJ Villadsen R Gudjonsson T Petersen OW 《Journal of mammary gland biology and neoplasia》2005,10(1):61-74
Recent genome-wide expression analysis of breast cancer has brought new life to the classical idea of tumors as caricatures of the process of tissue renewal as envisioned by Pierce and Speers (Cancer Res 1988;48:1996–2004) more than a decade ago. The search for a cancer founder cell or different cancer founder cells is only possible if a hierarchy of differentiation has been established for the particular tissue in question. In the human breast, the luminal epithelial and myoepithelial lineages have been characterized extensively in situ by increasingly elaborate panel of markers, and methods to isolate, culture, and clone different subpopulations have improved dramatically. Comparisons have been made with the mouse mammary gland in physiological three-dimensional culture assays of morphogenesis, and the plasticity of breast epithelial cells has been challenged by immortalization and transformation. As a result of these efforts, several candidate progenitor cells have been proposed independently of each other, and some of their features have been compared. This research has all been done to better understand breast tissue homeostasis, cell-type diversification in general and breast cancer evolution in particular. The present review discusses the current approaches to address these issues and the measures taken to unravel and maintain cell type diversification for further investigation. 相似文献
18.
19.
Wei PL Kuo LJ Huang MT Ting WC Ho YS Wang W An J Chang YJ 《Annals of surgical oncology》2011,18(6):1782-1790
Background
Long-term cigarette smoking increases the risk of colorectal cancer mortality. Tobacco’s addictive toxin, nicotine, was reported to increase DNA synthesis of colon cancer cells. Because metastasis is the major cause of cancer death, the influence of nicotine on the migration of colon cancer cells remains to be determined.Methods
The influence of nicotine on the migration of colon cancer cells was evaluated using transwell assay. Nicotine receptor-mediated migration was studied by using both inhibitors and small interfering RNA (siRNA). The role of COX-2 signal was studied using pharmacological inhibitors. The expression of epithelial mesenchymal transition (EMT) marker and COX-2 signal was evaluated using real-time polymerase chain reaction (PCR).Results
Nicotine enhanced DLD-1 and SW480 cell migration in a dose-dependent manner. We used inhibitors and siRNA to demonstrate that α7-nAChR mediates nicotine-enhanced colon cancer cell migration and upregulates fibronectin expression, which is involved in nicotine-enhanced migration. Furthermore, COX-2 signal was induced by nicotine treatment and is involved in nicotine-enhanced fibronectin expression.Conclusions
Nicotine, tobacco’s additive toxin, enhances colon cancer metastasis through α7-nAChR and fibronectin—a mesenchymal marker for epithelial mesenchymal transition. Furthermore, COX-2 signal was involved in the induction of fibronectin. Therefore, smoking may play role in the progression of colon cancer. 相似文献20.
Rojas-Sanchez Guadalupe García-Miranda Alin Montes-Alvarado José Benito Cotzomi-Ortega Israel Sarmiento-Salinas Fabiola Lilí Jimenez-Ignacio Eduardo Eleazar Ramírez-Ramírez Dalia Romo-Rodríguez Rubí Esmeralda Reyes-Leyva Julio Vallejo-Ruiz Verónica Pazos-Salazar Nidia Gary Maycotte Paola 《Journal of mammary gland biology and neoplasia》2021,26(4):341-355