Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The spread of cancer cells to regional lymph nodes through the lymphatic system is the first step in the dissemination of breast cancer. In several human cancers including those of the breast and prostate, the expression of vascular endothelial growth factor C (VEGF-C) is associated with lymph node metastasis. Our study was undertaken to evaluate the effect of VEGF-C on metastasis of poorly invasive, estrogen dependent human MCF-7 breast cancer cells. MCF-7 breast cancer cells transfected with VEGF-C (MCF-7-VEGF-C) were grown as tumors in the mammary fat pads of nude mice implanted with subcutaneous estrogen pellets. Tumor lymphangiogenesis and lymph node metastasis were studied immunohistochemically using antibodies against lymphatic vessel hyaluronan receptor -1 (LYVE-1), VEGF receptor-3 (VEGFR-3), PECAM-1, pan-cytokeratin and estrogen dependent pS2 protein. Overexpression of VEGF-C in transfected MCF-7 cells stimulated in vivo tumor growth in xenotransplanted mice without affecting estrogen responsiveness. The resulting tumors metastasized to the regional lymph nodes in 75% (in 6 mice out of 8, Experiment I) and in 62% (in 5 mice out of 8, Experiment II) of mice bearing orthotopic tumors formed by MCF-7-VEGF-C cells whereas no metastases were observed in mice bearing tumors of control vector-transfected MCF-7 cells (MCF-7-Mock). The density of intratumoral and peritumoral lymphatic vessels was increased in tumors derived from MCF-7-VEGF-C cells but not MCF-7-Mock cells. Taken together, our results show that VEGF-C overexpression stimulates tumor lymphangiogenesis and induces normally poorly metastatic estrogen-dependent MCF-7 tumors to disseminate to local lymph nodes. These data suggest that VEGF-C has an important role in lymph node metastasis of breast cancer even at its hormone-dependent early stage.
 ...
PMID:VEGF-C induced lymphangiogenesis is associated with lymph node metastasis in orthotopic MCF-7 tumors. 1194 78

Lymphatic vessels play a crucial role in a variety of human cancers, since invasion of lymphatic vessels by tumor cells and subsequent development of lymph node metastases significantly influences prognosis of cancer patients and therefore represent an integral part of tumor staging. Recent evidence on the important influence of lymphangiogenetic growth factors on intralymphatic cancer growth and metastasis raises hopes that lymphatic vessels and factors inducing their growth could serve as an additional target for tumor therapy. Nevertheless, in contrast to blood vessel angiogenesis, the mechanisms of new lymphatic vessel formation in human cancers, i.e. lymphangiogenesis, are still relatively unclear. In addition, only little data exist so far on the quantification and impact of this lymphangiogenesis, evident by lymphatic microvessel density (LMVD), on the prognosis of cancer patients. With expectation of possible anti-lymphangiogenic therapies, this review focuses on the mechanisms of lymphangiogenesis in general, and especially on the role of lymphatic vessels in gynecological and breast cancer, which are the so far most detailed investigated malignancies with regard to lymphangiogenesis.
 ...
PMID:Lymphatic vessels and lymphangiogenesis in female cancer: mechanisms, clinical impact and possible implications for anti-lymphangiogenic therapies (Review). 1195 9

Expression of angiogenic and lymphangiogenic factors by tumors may influence the route of metastatic spread. The angiogenic factor vascular growth factor-C (VEGF-C) is implicated in the development of lymphatic vessels and promotion of lymphatic metastasis. The purpose of this study was to determine whether VEGF-C correlates with lymph node metastasis or prognosis. We assessed VEGF-C expression using immunohistochemistry in 123 invasive breast carcinomas with long-term follow-up. The relationship between VEGF-C expression and lymph node status and other established clinicopathological parameters was assessed. Whether VEGF-C expression plays a prognostic role in breast cancer was also investigated. VEGF-C expression was identified in 103 cases (83.7%). Positive VEGF-C was significantly correlated with lymph node metastasis (P = 0.0131). Survival curves determined by the Kaplan-Meier method and univariate analysis demonstrated that positive VEGF-C was associated with both disease-free survival (P = 0.0165) and overall survival (P = 0.0175). On the basis of our findings, VEGF-C plays a crucial role in lymph node metastasis and may be a significant prognostic factor for long-term survival in breast cancer.
 ...
PMID:Clinicopathological significance of vascular endothelial growth factor-C in breast carcinoma with long-term follow-up. 1269 95

Human inflammatory breast carcinoma (IBC) is the most malignant type of breast cancer with an extremely poor prognosis. The dog is the unique animal species in which spontaneous inflammatory mammary carcinoma (IC) has been reported, although it is not well documented. The purpose of this study was to characterize histopathologically and immunohistochemically the canine IC, considering associated clinical features. Twenty-one dogs diagnosed with IC and with known clinical and necropsy data were included in the study. Tissue samples from necropsies underwent a histopathological review and an immunohistochemical study (Ki-67, estrogen receptor (ER), progesterone receptor (PR), and P53 tumor suppressor protein). The histological study revealed several types of carcinomas (solid, tubular, papillary, and adenosquamous) and three lipid-rich carcinomas. All tumors were ER negative. Two histological patterns of neoplastic dermal infiltration were observed: tubular/papillary and sarcomatous-like. Dermal sarcomatous-like infiltration was significantly related to previous treatments with progestagens (p = 0.006), primary type of IC (p = 0.03), extreme local pain (p = 0.02), reduced observation of emboli in dermal lymphatic vessels (p = 0.01), and increased expression of p53 (p = 0.001). PR expression was significantly higher in secondary post-surgical IC (p = 0.04). The absence of PR was related to the existence of pulmonary metastases at necropsy (p = 0.04). Canine primary IC is the most aggressive form of this disease with distinct histopathological and immunohistochemical characteristics. Progestins and endocrine-related mechanisms seem to be involved in canine IC development. Canine IC could serve as a spontaneous model for human IBC, particularly in studies concerned with new therapeutics approaches.
Breast Cancer Res Treat 2003 Mar
PMID:Canine inflammatory mammary carcinoma: histopathology, immunohistochemistry and clinical implications of 21 cases. 1272 14

Lymphoscintigraphy involves interstitial injection of radiolabelled particulate materials or radioproteins. Although several variations in the technique have been described, their place in clinical practice remains controversial. Traditional diagnostic criteria are based primarily on lymph node appearances but in situations such as breast cancer, where lymph nodes may have been excised, these criteria are of limited use. In these circumstances, lymphatic vessel morphology takes on greater importance as a clinical endpoint, so a method that gives good definition of lymphatic vessels would be useful. In patients with breast cancer, for example, such a method, used before and after lymph node resection, may assist in predicting the development of breast cancer-related lymphoedema. The aim of this study was to optimise a method for the visualisation of lymphatic vessels. Subcutaneous (sc) and intradermal (id) injection sites were compared, and technetium-99m nanocolloid, a particulate material, was compared with (99m)Tc-human immunoglobulin (HIG), which is a soluble macromolecule. Twelve normal volunteers were each studied on two occasions. In three subjects, id (99m)Tc-HIG was compared with sc (99m)Tc-HIG, in three id (99m)Tc-nanocolloid was compared with sc (99m)Tc-nanocolloid, in three id (99m)Tc-HIG was compared with id (99m)Tc-nanocolloid and in three sc (99m)Tc-HIG was compared with sc (99m)Tc-nanocolloid. Endpoints were quality of lymphatic vessel definition, the time after injection at which vessels were most clearly visualised, the rate constant of depot disappearance ( k) and the systemic blood accumulation rate as measured by gamma camera imaging over the liver or cardiac blood pool. Excellent definition of lymphatic vessels was obtained following id injection of either radiopharmaceutical, an injection route that was clearly superior to sc. Differences between radiopharmaceuticals were less clear, although after id injection, (99m)Tc-HIG gave images that were marginally but significantly better than those given by (99m)Tc-nanocolloid. Image quality correlated inversely with time after injection at which the best image was obtained, consistent with the notion that good vessel definition was dependent on a "narrow" bolus width. k was approximately three times higher after id injection than after sc injection but it was not significantly different between radiopharmaceuticals for either injection route. Intradermal (99m)Tc-HIG gave a cardiac blood pool signal that, over the first 60 min, increased about five times faster than that with sc (99m)Tc-HIG, but no clear difference was observed in the rate of increase in hepatic activity between id (99m)Tc-nanocolloid and sc (99m)Tc-nanocolloid. We conclude that id injection provides rapid access of radiotracers to lymphatic vessels, which is ideal for imaging lymphatic vessel morphology. (99m)Tc-HIG is marginally superior to nanocolloid for this purpose and, in drainage basins from which lymph nodes have been excised, is not handicapped by a potentially inferior ability, compared with radiocolloid, to image lymph nodes.
 ...
PMID:Finding an optimal method for imaging lymphatic vessels of the upper limb. 1472 73

Endothelial cells line the inside of blood and lymphatic vessels, and cancer cells must cross this barrier, first to gain access to the circulation, and, second, to exit and metastasize. How this occurs is incompletely understood. We now demonstrate that human cancer cells are able to fuse with endothelial cells to form hybrid cells displaying proteins and chromosomal markers characteristic of both parent cells. The hybrid cells are viable and capable of undergoing mitosis. Fusions between cancer cells and endothelial cells were shown to occur both in vitro, in co-cultures of human breast cancer cells and endothelial cells, and in vivo, following intravascular dissemination of human breast cancer cells in nude mice. These observations demonstrate a new type of cancer-endothelial cell interaction that may be of fundamental importance to the process of metastasis.
 ...
PMID:Spontaneous fusion between cancer cells and endothelial cells. 1531 61

Noninvasive imaging techniques to image and characterize delivery and transport of macromolecules through the extracellular matrix (ECM) and supporting stroma of a tumor are necessary to develop treatments that alter the porosity and integrity of the ECM for improved delivery of therapeutic agents and to understand factors which influence and control delivery, movement, and clearance of macromolecules. In this study, a noninvasive imaging technique was developed to characterize the delivery as well as interstitial transport of a macromolecular agent, albumin-GdDTPA, in the MCF-7 human breast cancer model in vivo, using magnetic resonance imaging. The transport parameters derived included vascular volume, permeability surface area product, macromolecular fluid exudate volume, and drainage and pooling rates. Immunohistochemical staining for the lymphatic endothelial marker LYVE-1 was done to determine the contribution of lymphatics to the macromolecular drainage. Distinct pooling and draining regions were detected in the tumors using magnetic resonance imaging. A few lymphatic vessels positively stained for LYVE-1 were also detected although these were primarily collapsed and tenuous suggesting that lymphatic drainage played a minimal role, and that the bulk of drainage was due to convective transport through the ECM in this tumor model.
 ...
PMID:Characterizing extravascular fluid transport of macromolecules in the tumor interstitium by magnetic resonance imaging. 1573 30

Metastasis to the regional lymph nodes through the lymphatic vessels is a common step in the progression of cancer and an important prognostic factor in many types of cancer. Recent evidence suggests that VEGF-C promotes lymphangiogenesis, and that tumor lymphangiogenesis in turn promotes lymphatic metastasis. We have studied the role of LVD in breast cancer, and examined whether LVD is associated with lymph node metastasis, VEGF-C expression, or prognosis. In addition, we examined whether VEGF-C mRNA transcript levels were associated with lymph node metastasis and LVD. We began by investigating the lymphatics in primary human breast carcinoma with long-term follow-up (113 cases of invasive ductal and other breast cancers) by quantitative immunohistochemical staining for podoplanin. We then analyzed the relationship between LVD and lymph node status as well as VEGF-C immunoreactivity and other established clinicopathological parameters. The relationship between LVD and prognosis was also studied. VEGF-C mRNA transcript levels were examined by quantitative real-time RT-PCR, in 55 invasive ductal breast carcinomas. This was followed by an analysis of the relationship between VEGF-C mRNA transcript levels and lymph node metastasis as well as LVD. Mean LVD of 'hot spots' was 10.2 +/- 7.4/each case. LVD was significantly correlated with lymph node metastasis (p < 0.0001), VEGF-C immunoreactivity (p = 0.0084), and podoplanin positive lymphatic invasion (p < 0.0001). Survival curves determined by the Kaplan-Meier method and univariate analysis demonstrated that high LVD was associated with both worse disease free survival (p = 0.0033) and overall survival (p = 0.0391). VEGF-C mRNA transcript levels were also correlated with lymph node metastasis (p = 0.0074) and LVD (p = 0.0409). Increased LVD was correlated with lymph node metastasis and VEGF-C expression. High LVD may be a significant unfavorable prognostic factor for long-term survival in breast cancer.
Breast Cancer Res Treat 2005 May
PMID:Lymph vessel density correlates with nodal status, VEGF-C expression, and prognosis in breast cancer. 1586 40

Lymphangiogenesis is key to the lymphatic spread of cancer cells. The current study examined the potential effect of hepatocyte growth factor (HGF), a factor known to have strong biological effects on endothelial cells, on the lymphangiogenic function of endothelial cells and the formation of lymphatic vessels using both in vitro and in vivo models. Human endothelial cells that have lymphatic characteristics, human prostate and breast cancer cells PC-3 and MDA MB 231, were used. Expression of lymphatic markers, podoplanin, Prox-1, vascular endothelial growth factor receptor 3 (VEGF-R3) and LYVE-1 was determined using reverse transcription polymerase reaction and quantitative PCR. In nude mice prostate and breast xenograft tumour models, either HGF or an HGF-producing fibroblast cell line MRC-5 was given with or without the HGF antagonist, NK4. The lymphangiogenic marker and lymphatic vessels in tumour tissues were also assessed using quantitative PCR and immunohistochemistry, respectively. In the mice tumour models, infusion of rhHGF significantly increased the levels of podoplanin and LYVE-1 in the tumour (p=0.05 for podoplanin and p<0.05 for LYVE-1 vs. without HGF in the prostate tumour model, p<0.05 for podoplanin and p<0.01 for LYVE-1 vs. without HGF for the breast tumour model; p<0.05 for podoplanin and p<0.01 for LYVE-1 vs. without HGF in the breast tumour model). The increased level of LYVE-1 transcript was supported by an increase in the number of LYVE-1-positive lymphatic vessels in tumours, using immunohistochemical analysis. Co-injection of MRC5 cells also increased the levels of LYVE-1 and number of LYVE-1-positive vessels in tumour tissues. The effects of HGF and MRC5 were significantly reduced by the HGF antagonist, NK4. In the in vitro models, rhHGF significantly increased the level of both podoplanin and LYVE-1, as shown by quantitative PCR analysis. Hepatocyte growth factor has potential lymphangiogenic activities, and this may have important implications in the nodal spread of cancer cells.
 ...
PMID:The potential lymphangiogenic effects of hepatocyte growth factor/scatter factor in vitro and in vivo. 1614 11

Breast cancer often spreads from the primary tumor to regional lymph nodes. Lymph node status provides clinically important information for making treatment decisions. Spread via lymphatics is also important for the biology of breast cancer, as tumor cells in lymph nodes may provide a reservoir of cells leading to distant, lethal metastases. Improved understanding of the biology of lymphatic spread thus is important for improved breast cancer survival. Advances towards understanding the interactions between tumors cells and lymphatic vessels have in part been limited by the lack of suitable cell lines and experimental models. We have addressed this need by developing a new model of lymphatic metastasis. Here we describe the establishment of 468LN cells, a variant of the MDA-MB-468 human breast adenocarcinoma cell line, which produces extensive lymph node metastasis following orthotopic injection of nude mice. 468LN cells are also more aggressive in vitro, produce more osteopontin and express different surface integrins compared to the parent line. The dramatic in vitro and in vivo phenotypic and molecular differences of 468LN and parental 468GFP cells make this pair of cell lines a unique model for the specific study of lymph node metastasis of breast cancer.
 ...
PMID:A new model for lymphatic metastasis: development of a variant of the MDA-MB-468 human breast cancer cell line that aggressively metastasizes to lymph nodes. 1617 Jun 71


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>