Fluorescent LYVE-1 Antibody to Image Dynamically Lymphatic Trafficking of Cancer Cells In Vivo

McElroy, Michele; Hayashi, Katsuhiro; Garmy‐Susini, Barbara; Kaushal, Sharmeela; Varner, Judith A.; Moossa, A. R.; Hoffman, Robert M.; Bouvet, Michael

doi:10.1016/j.jss.2007.12.769

Cited by 45 publications

(45 citation statements)

References 26 publications

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“…Thus, in most previous papers, fluid drainage pathways in LNs and lymphatic vessels has been studied using interstitial/intradermal injections: from the chin to the neck and cervical LNs [15]; from the middle phalanges of the upper extremities to the axillary LN [16]; from the footpad to the popliteal LN [17,18]; from the tissue around the exposed SiLN to the PALN [19]; from the hindfoot to the PALN [20]; from the tail to the ischial nodes [21]; and from the footpad to the the axillary node [21]. Using these approaches, it would take a considerable time to capture the filling of entire lymphatic vessels with tracers because the lymph velocity is less than 10 μm/s [22].…”

Section: Discussionmentioning

confidence: 99%

Visualization of fluid drainage pathways in lymphatic vessels and lymph nodes using a mouse model to test a lymphatic drug delivery system

Kodama

Hatakeyama

Kato

et al. 2014

Biomed. Opt. Express

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Curing/preventing micrometastasis to lymph nodes (LNs) located outside the surgically resected area is essential for improving the morbidity and mortality associated with breast cancer and head and neck cancer. However, no lymphatic therapy system exists that can deliver drugs to LNs located outside the dissection area. Here, we demonstrate proof of concept for a drug delivery system using MXH10/Mo-lpr/lpr mice that exhibit systemic lymphadenopathy, with some peripheral LNs being as large as 10 mm in diameter. We report that a fluorescent solution injected into the subiliac LN (defined as the upstream LN within the dissection area) was delivered successfully to the proper axillary LN (defined as the downstream LN outside the dissection area) through the lymphatic vessels. Our results suggest that this approach could be used before surgical resection to deliver drugs to downstream LNs outside the dissection area. We anticipate that our methodology could be applied clinically, before surgical resection, to cure/prevent micrometastasis in LNs outside the dissection area, using techniques such as ultrasound-guided internal jugular vein catheterization.

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Section: Discussionmentioning

confidence: 99%

Visualization of fluid drainage pathways in lymphatic vessels and lymph nodes using a mouse model to test a lymphatic drug delivery system

Kodama

Hatakeyama

Kato

et al. 2014

Biomed. Opt. Express

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“…Fluorescent labeling of LYVE-1, a lymphatic endothelial cell receptor that lines lymphatic vessels, is the most widely used technique for the assessment of tumor cell migration via the lymphatic system (63). However, in vivo application of this process is prone to cytotoxicity, immune responses, photobleaching, blinking or strong light scattering, and background auto-fluorescence.…”

Section: Clinical Significance Of the Lymphatic Systemmentioning

confidence: 99%

Breast cancer metastasis and the lymphatic system

Rahman

Mohammed

2015

Oncology Letters

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Abstract. Breast cancer remains the leading cause of cancer mortality worldwide, despite a significant decline in death rates due to early detection. The majority of cancer mortalities are due to the metastasis of tumor cells to other organs. Metastasis or tumor cell dissemination occurs via the hematogenous and lymphatic systems. For many carcinomas, the dissemination of tumor cells via lymphatic drainage of the tumor is the most common metastatic route. Such lymphatic drainage collects at the regional lymph nodes and the dissection and pathological examination of these nodes for lodged cancer cells is the gold standard procedure to detect metastasis. The present report provides an overview of the lymphatic system and its clinical significance as a prognostic factor, in addition to the interactions between the primary tumor and its microenvironment, and the influence of genomic subtypes on the resulting organ-specific pattern of tumor cell dissemination. It also examines the seemingly protracted asymptomatic period, during which the disseminated cells remain dormant, leading to the manifestation of metastasis decades after the successful treatment of the primary tumor.

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“…LYVE1 is an integral membrane glycoprotein that is used as a marker of lymphatic vessels (50,51). Relative to its expression in normal liver, LYVE1 shows progressive down-regulation from polyclonal cirrhotic nodules to monoclonal cirrhotic nodules to HCC (52).…”

Section: Discussionmentioning

confidence: 99%

Involvement of Insulin-like Growth Factor-binding Protein-3 in the Effects of Histone Deacetylase Inhibitor MS-275 in Hepatoma Cells

Lin

Martin

Marsh

et al. 2011

Journal of Biological Chemistry

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Insulin-like growth factor-binding protein-3 (IGFBP-3mRNA levels almost 80% lower in hepatoma tissues than in normal liver. The decreased IGFBP-3 expression has been associated with epigenetic changes such as DNA methylation and histone deacetylation (3, 4). IGFBP-3 is the most abundant insulin-like growth factor-binding protein in the human circulation, where it forms part of the IGF transport complex that stabilizes IGF-I and IGF-II and limits their access to tissues (5). In addition to its transport function, IGFBP-3 also has multiple biological roles at the cellular level, which depend on its interaction with a wide range of ligands (6, 7). By virtue of its ability to bind IGF-I and IGF-II with high affinity, IGFBP-3 can inhibit signaling through the type I IGF receptor. Other functions, independent of IGF binding, include effects on apoptosis, cell growth, differentiation, and migration, many of which appear dependent on the cell type and context (8 -10). For example, IGFBP-3 can induce apoptosis in various cancer cell models, including prostate and breast cancer (11, 12), although it can also have growth-stimulatory effects (13).Whereas in the rodent liver, IGFBP-3 gene expression is predominantly confined to Kupffer cells (14), in human liver, IGFBP-3 is synthesized by hepatocytes (15) and has been proposed to function as an inhibitor of cell proliferation in hepatocellular carcinoma (HCC) 4 (3, 16). MS-275 is a histone deacetylase inhibitor for which a significant anti-cancer role has been demonstrated in vitro and in vivo (17,18). In this study, we have investigated the involvement of endogenous IGFBP-3 in the anti-tumor effects of MS-275, by down-regulating its expression using siRNA. We describe roles for IGFBP-3 in hepatoma cell proliferation and migration, and we identify IGFBP-3-dependent proteins involved in mediating these effects. EXPERIMENTAL PROCEDURESMaterials-Cell culture reagents were from Invitrogen. MS-275, trypan blue, propidium iodide, and RNase were purchased from Sigma. Chemically synthesized siRNA against IGFBP-3, THBS2, and LYVE1 and an IGFBP-3 scrambled control were from Qiagen (Doncaster, Victoria, Australia). Recombinant human IGFBP-3 was produced in 911 human retinoblastoma cells (19). The following antibodies were purchased for Western analysis: histone H3, histone H3-acetyl-LYS 9/18, his-

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Fluorescent LYVE-1 Antibody to Image Dynamically Lymphatic Trafficking of Cancer Cells In Vivo

Cited by 45 publications

References 26 publications

Visualization of fluid drainage pathways in lymphatic vessels and lymph nodes using a mouse model to test a lymphatic drug delivery system

Visualization of fluid drainage pathways in lymphatic vessels and lymph nodes using a mouse model to test a lymphatic drug delivery system

Breast cancer metastasis and the lymphatic system

Involvement of Insulin-like Growth Factor-binding Protein-3 in the Effects of Histone Deacetylase Inhibitor MS-275 in Hepatoma Cells

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