Abstract：
:Tumor spread involves degradation of various components of the extracellular matrix and blood vessel wall. Among these is heparan sulfate proteoglycan, which plays a key role in the self-assembly, insolubility and barrier properties of basement membranes and extracellular matrices. Expression of an endoglycosidase (heparanase) which degrades heparan sulfate correlates with the metastatic potential of tumor cells, and treatment with heparanase inhibitors markedly reduces the incidence of metastasis in experimental animals. Heparin-binding angiogenic proteins are stored as a complex with heparan sulfate in the microenvironment of tumors. These proteins are released and can induce new capillary growth when heparan sulfate is degraded by heparanase. Here, we describe the molecular properties, expression and involvement in tumor progression of a human heparanase. The enzyme is synthesized as a latent approximately 65 kDa protein that is processed at the N-terminus into a highly active approximately 50 kDa form. The heparanase mRNA and protein are preferentially expressed in metastatic human cell lines and in tumor biopsy specimens, including breast carcinoma. Overexpression of the heparanase cDNA in low-metastatic tumor cells conferred a high metastatic potential in experimental animals, resulting in an increased rate of mortality. The heparanase enzyme also released ECM-resident bFGF in vitro, and its overexpression elicited an angiogenic response in vivo. Heparanase may thus facilitate both tumor cell invasion and neovascularization, two critical steps in tumor progression. Mammary glands of transgenic mice overexpressing the heparanase enzyme exhibit precocious branching of ducts and alveolar development, suggesting that the enzyme promotes normal morphogenesis and possibly pre-malignant changes in the mammary gland.
journal_name
J Mammary Gland Biol Neoplasiajournal_title
Journal of mammary gland biology and neoplasiaauthors
Zcharia E,Metzger S,Chajek-Shaul T,Friedmann Y,Pappo O,Aviv A,Elkin M,Pecker I,Peretz T,Vlodavsky Idoi
10.1023/a:1011375624902subject
Has Abstractpub_date
2001-07-01 00:00:00pages
311-22issue
3eissn
1083-3021issn
1573-7039journal_volume
6pub_type
杂志文章,评审abstract：:Mammalian cells depend on phospholipid (PL) and fatty acid (FA) transport to maintain membrane structure and organization, and to fuel and regulate cellular functions. In mammary glands of lactating animals, copious milk secretion, including large quantities of lipid in some species, requires adaptation and integratio...
journal_title：Journal of mammary gland biology and neoplasia
pub_type： 杂志文章,评审
doi：10.1007/s10911-014-9318-8
更新日期：2014-03-01 00:00:00
abstract：: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 th...
journal_title：Journal of mammary gland biology and neoplasia
pub_type： 杂志文章,评审
doi：10.1023/B:JOMG.0000017431.45314.07
更新日期：2003-10-01 00:00:00
abstract：: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 go...
journal_title：Journal of mammary gland biology and neoplasia
pub_type： 杂志文章,评审
doi：10.1007/s10911-011-9207-3
更新日期：2011-06-01 00:00:00
abstract：:The mouse model for breast cancer has developed into a most effective means of dissecting and understanding this devastating disease. The inbred transgenic mouse lends itself to biological, molecular, immunological, and genetic studies. The observation, dissection, transplantation, and subsequent amplification of prec...
journal_title：Journal of mammary gland biology and neoplasia
pub_type： 杂志文章,评审
doi：10.1007/s10911-008-9088-2
更新日期：2008-09-01 00:00:00
abstract：:Insulin-like growth factor-I and -II (IGF-I and IGF-II) and/or the type I insulin-like growth factor receptor (IGF-IR) have been implicated in a number of human tumors including breast cancer. However, despite being implicated in breast cancer for approximately 25 years and given that transgenic technology has been av...
journal_title：Journal of mammary gland biology and neoplasia
pub_type： 杂志文章,评审
doi：10.1007/s10911-008-9097-1
更新日期：2008-12-01 00:00:00
abstract：:The insulin-like growth factors (IGFs) signaling via the type I insulin-like growth factor receptor (IGF-1R) regulate multiple aspects of malignancy. The importance of IGF-1R in regulating the malignant phenotype is currently being validated in numerous clinical trials for cancer including breast cancer. This review d...
journal_title：Journal of mammary gland biology and neoplasia
pub_type： 杂志文章,评审
doi：10.1007/s10911-008-9105-5
更新日期：2008-12-01 00:00:00
abstract：:Breast cancer is one of the most common cancers of women in the Western world. Despite modest achievements in the treatment of this disease, there is a substantial unmet medical need to reduce the occurrence of new breast cancers. In several prospective, placebo-controlled trials, the antiestrogen tamoxifen has been s...
journal_title：Journal of mammary gland biology and neoplasia
pub_type： 杂志文章,评审
doi：10.1023/a:1025727103811
更新日期：2003-01-01 00:00:00
abstract：:With the discovery of an activated Notch oncogene as a causative agent in mouse mammary tumor virus induced breast cancer in mice, the potential role for Notch signaling in normal and pathological mammary development was revealed. Subsequently, Notch receptors have been found to regulate normal development in many org...
journal_title：Journal of mammary gland biology and neoplasia
pub_type： 杂志文章,评审
doi：10.1023/B:JOMG.0000037159.63644.81
更新日期：2004-04-01 00:00:00
abstract：:Breast cancer (BC) is a leading cause of death among women with malignant diseases. The selection of adequate therapies for highly invasive and metastatic BCs still represents a major challenge. Novel combinatorial therapeutic approaches are urgently required to enhance the efficiency of BC treatment. Recently, microR...
journal_title：Journal of mammary gland biology and neoplasia
pub_type： 杂志文章,评审
doi：10.1007/s10911-021-09478-3
更新日期：2021-01-21 00:00:00
abstract：:Ductal development in the pubertal mouse mammary gland is characterized by dramatic morphological changes in the epithelium driven by proliferation of cap and body cells in the terminal endbuds. Recent experiments revealed a coincident and abundant apoptosis in the body cells of these structures. The cells undergoing ...
journal_title：Journal of mammary gland biology and neoplasia
pub_type： 杂志文章,评审
doi：10.1023/a:1018733426625
更新日期：1999-04-01 00:00:00
abstract：:Wild-type p53 is a tumor suppressor gene that plays a central role in maintaining the genetic integrity of the cell by preventing cells with damaged DNA from further proliferation. Mutation and deletion of p53 are the most common genetic defects seen in clinical cancer. About 40% of breast carcinomas show high levels ...
journal_title：Journal of mammary gland biology and neoplasia
pub_type： 杂志文章,评审
doi：10.1007/BF02013640
更新日期：1996-04-01 00:00:00
abstract：:Normal mammary gland development is the result of complex interactions between a number of hormones and growth factors. Normal and malignant human mammary epithelial cells are able to synthesize and to respond to various different, locally acting growth factors and growth inhibitors. Among these, the EGF-related pepti...
journal_title：Journal of mammary gland biology and neoplasia
pub_type： 杂志文章,评审
doi：10.1023/a:1026351730785
更新日期：1997-04-01 00:00:00
abstract：:It has long been appreciated that the estrogen receptor (ER) plays an important role in the biology of breast cancer. It is an accepted factor predicting favorable disease outcome and treatment response, and as such is generally considered to represent a "good" prognostic marker in breast cancer. In this review we pre...
journal_title：Journal of mammary gland biology and neoplasia
pub_type： 杂志文章,评审
doi：10.1023/a:1014782813943
更新日期：2001-10-01 00:00:00
abstract：:Inflammation of the adipose tissues occurs in association with obesity. This inflammatory process leads to the induction of cyclooxygenase-2 (COX-2) expression and a consequent elevation in prostaglandin (PG) production, which, together with proinflammatory cytokines, induce aromatase expression and estrogen synthesis...
journal_title：Journal of mammary gland biology and neoplasia
pub_type： 杂志文章,评审
doi：10.1007/s10911-013-9299-z
更新日期：2013-12-01 00:00:00
abstract：:The microenvironment of a tumor has emerged recently as a critical contributor to the development of cancer. Within this environment, fibroblasts and immune cells are the cell lineages that seem to be active mediators of tumour development. The activated fibroblasts that are also present during wound healing and chron...
journal_title：Journal of mammary gland biology and neoplasia
pub_type： 杂志文章,评审
doi：10.1007/s10911-014-9326-8
更新日期：2014-07-01 00:00:00
abstract：:The centrosome is the major microtubule organizing center of the cell and as such it plays an important role in cytoskeletal organization and in the formation of the bipolar mitotic spindle. Centrosome defects, characterized by abnormal size, number, and microtubule nucleation capacity, are distinguishing features of ...
journal_title：Journal of mammary gland biology and neoplasia
pub_type： 杂志文章,评审
doi：10.1023/a:1011312808421
更新日期：2001-04-01 00:00:00
abstract：:T cell immunity in breast cancer is suggested to play a role in tumor dormancy, a period of stability which can correspond to the time interval between primary treatment and tumor recurrence. Bone marrow in breast cancer patients seems to be particularly important because it is highly enriched with cancer specific mem...
journal_title：Journal of mammary gland biology and neoplasia
pub_type： 杂志文章,评审
doi：10.1023/a:1020308104613
更新日期：2002-04-01 00:00:00
abstract：:We have reported the use of vectors based on avian leukosis virus (ALV) and ALV env pseudotyped lentivirus for stably introducing genes into somatic mammary cells in vivo for tumor modeling. These vectors require tva transgenic mice for viral infection. Here, we report, and described the method for, stably introducing...
journal_title：Journal of mammary gland biology and neoplasia
pub_type： 杂志文章
doi：10.1007/s10911-009-9154-4
更新日期：2009-12-01 00:00:00
abstract：: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 m...
journal_title：Journal of mammary gland biology and neoplasia
pub_type： 杂志文章,评审
doi：10.1007/s10911-012-9244-6
更新日期：2012-03-01 00:00:00
abstract：:The potential role of smoking in breast cancer risk has been the subject of over 100 publications, numerous scientific reviews, and animated debate. Tobacco exposure is a well-established cause of lung cancer, and is thought to account for nearly one third of all cancer deaths. Tobacco smoke contains thousands of chem...
journal_title：Journal of mammary gland biology and neoplasia
pub_type： 杂志文章,评审
doi：10.1007/s10911-012-9269-x
更新日期：2013-03-01 00:00:00
abstract：:The One Health concept promotes integrated evaluation of human, animal, and environmental health questions to expedite advances benefiting all species. A recognition of the multi-species impact of mastitis as a painful condition with welfare implications leads us to suggest that mastitis is an ideal target for a One H...
journal_title：Journal of mammary gland biology and neoplasia
pub_type： 杂志文章,评审
doi：10.1007/s10911-018-9395-1
更新日期：2018-06-01 00:00:00
abstract：:The Notch receptor protein and its signaling pathway have been well conserved throughout evolution and appear to be pivotal components in cell fate decisions during development. Recent studies suggest that, depending on the cellular and developmental context, Notch signaling may also affect cell proliferation and prog...
journal_title：Journal of mammary gland biology and neoplasia
pub_type： 杂志文章,评审
doi：10.1023/a:1009512414430
更新日期：2001-01-01 00:00:00
abstract：:The ErbB receptor tyrosine kinase family has often been associated with increased growth of breast epithelial cells, as well as malignant transformation and progression. In contrast, ErbB4/HER4 exhibits unique attributes from a two step proteolytic cleavage which releases an 80 kilodalton, nuclear localizing, tyrosine...
journal_title：Journal of mammary gland biology and neoplasia
pub_type： 杂志文章,评审
doi：10.1007/s10911-008-9080-x
更新日期：2008-06-01 00:00:00
abstract：:The mouse has emerged as a primary animal model for human breast cancer because the mammary glands of the two species are very similar in structure and function. In this regard the TDLU and LA have similar morphology. The mouse, infected by MMTV, develops "spontaneous" tumors with specific but limited tumor phenotypes...
journal_title：Journal of mammary gland biology and neoplasia
pub_type： 杂志文章,评审
doi：10.1023/a:1018712905244
更新日期：1999-01-01 00:00:00
abstract：:We review the role of Neuregulin 3 (Nrg3) and Erbb receptor signalling in embryonic mammary gland development. Neuregulins are growth factors that bind and activate its cognate Erbb receptor tyrosine kinases, which form a signalling network with established roles in breast development and breast cancer. Studies have s...
journal_title：Journal of mammary gland biology and neoplasia
pub_type： 杂志文章,评审
doi：10.1007/s10911-013-9286-4
更新日期：2013-06-01 00:00:00
abstract：:Obesity is a preventable risk factor for breast cancer following menopause. Regardless of menopausal status, obese women who develop breast cancer have a worsened prognosis. Breast tissue is comprised of mammary epithelial cells organized into ducts and lobules and surrounded by adipose-rich connective tissue. Studies...
journal_title：Journal of mammary gland biology and neoplasia
pub_type： 杂志文章,评审
doi：10.1007/s10911-020-09452-5
更新日期：2020-06-01 00:00:00
abstract：:Dynamic interactions between the hormone responsive mammary gland epithelium and surrounding stromal macrophage populations are critical for normal development and function of the mammary gland. Macrophages are versatile cells capable of diverse roles in mammary gland development and maintenance of homeostasis, and th...
journal_title：Journal of mammary gland biology and neoplasia
pub_type： 杂志文章,评审
doi：10.1007/s10911-014-9319-7
更新日期：2014-07-01 00:00:00
abstract：:This article illustrates the most common benign and malignant lesions in the breast, and is intended for the biologist working in the area of breast cancer and breast biology, not for the practicing pathologist. The atlas covers benign proliferative lesions, atypical lesions, variants of in situ cancer, the main types...
journal_title：Journal of mammary gland biology and neoplasia
pub_type： 杂志文章,评审
doi：10.1023/a:1026439204849
更新日期：2000-04-01 00:00:00
abstract：:Transforming growth factor beta (TGF-beta) receptor expression and signal transduction in human breast cancer are reviewed as a function of estrogen receptor (ER) expression. ER+ breast cancer cells are generally resistant to the inhibitory effects of TGF-beta. The only known exception appears to be MCF-7 early passag...
journal_title：Journal of mammary gland biology and neoplasia
pub_type： 杂志文章,评审
doi：10.1007/BF02017392
更新日期：1996-10-01 00:00:00
abstract：:The neuroendocrine hormone prolactin (PRL) stimulates breast growth and differentiation during puberty, pregnancy, and lactation. Despite extensive and convincing data indicating that PRL significantly contributes to the pathogenesis and progression of rodent mammary carcinoma, parallel observations for human breast c...
journal_title：Journal of mammary gland biology and neoplasia
pub_type： 杂志文章,评审
doi：10.1023/a:1026325630359
更新日期：1997-01-01 00:00:00
