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AlexaFluor 488-conjugated antibody against lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1)

Alexa488-Anti-LYVE-1
, PhD
National Center for Biotechnology Information, NLM, NIH, Bethesda, MD
Corresponding author.

Created: ; Last Update: July 6, 2011.

Chemical name:AlexaFluor 488-conjugated antibody against lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1)
Abbreviated name:Alexa488-Anti-LYVE-1
Synonym:
Agent category:Antibody
Target:Lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1)
Target category:Receptor
Method of detection:Optical, fluorescence imaging
Source of signal/contrast:AlexaFluor 488
Activation:No
Studies:
  • Checkbox In vitro
  • Checkbox Rodents
Structure is not available in PubChem.

Background

[PubMed]

The primary function of the lymphatic system is to drain ~10% of the interstitial fluid from small capillaries to lymphatic vessels through lymph nodes (LNs) and finally to the venous system (1-5). LNs form a natural filter for lymphatic drainage and prevent the possible migration of cancer cells from the lymphatic system into the body. As the first LN that receives lymph drainage from a tumor bed, the sentinel LN is very likely to contain cancer cells if the primary tumor has spread via the lymphatic system (1, 2). The lymphatic system is complex, and its detection and mapping remain challenging (1, 2, 6, 7). However, with advances of new imaging agents and techniques, imaging and mapping of both the lymphatic vessels and the LNs are now possible with x-ray–computed tomography, ultrasound, nuclear medicine, and magnetic resonance imaging (7-9). There is increasing evidence that tumor cells induce lymphangiogenesis in tumor-draining LNs in experimental models of cancer (10, 11) as well as in LNs of patients with metastatic melanoma and breast cancer (12, 13). Therefore, LN lymphangiogenesis might provide a target to image the early stages of tumor metastasis. In addition, chronic inflamed tissues produce vascular endothelial growth factor to induce lymphangiogenesis in draining LNs.

Hyaluronan (HA) is an abundant extracellular matrix glycosaminoglycan in skin and mesenchymal tissues, where it facilitates cell migration during inflammation, wound healing, metastasis, and embryonic morphogenesis (14, 15). CD44 is an integral cell membrane glycoprotein on leukocytes and has an important role in matrix adhesion lymphocyte activation and LN homing (16). CD44 binds HA to induce extravasation of lymphoid cells. Lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) has a 41% homology to CD44, and LYVE-1 expression is largely restricted to endothelial cells of lymphatic vessels and splenic sinusoidal endothelial cells. Expression was undetectable on lymphocytes, hematopoietic cells, or vascular endothelial cells. McElroy et al. (17) used AlexaFluor 488-conjugated antibody against LYVE-1 (Alexa488-anti-LYVE-1) for in vivo fluorescence imaging of lymphatic vessels and tumor cell trafficking.

Synthesis

[PubMed]

Anti-mouse LYVE-1 rat antibody (6.6 nmol, clone 223322, R&D Systems) was conjugated with AlexaFluor 488 tetrafluorophenyl ester in sodium bicarbonate buffer (pH 8) for 60 min at room temperature (17). Alexa488-anti-LYVE-1 was purified on a column by centrifugation. Control Alexa488-IgG was prepared similarly. There were approximately four dye moieties per antibody. Alexa488-anti-LYVE-1 immunoreactivity was not reported.

In Vitro Studies: Testing in Cells and Tissues

[PubMed]

No publication is currently available.

Animal Studies

Rodents

[PubMed]

McElroy et al. (17) injected ~0.02 nmol Alexa488-anti-LYVE-1 into tissues around the mammary inguinal LN in nude mice (n = 3). The inguinal LN, draining lymphatics, and axillary LN were imaged using a small-animal fluorescence imaging system at 0, 4, 12, 24, 36, 48, and 72 h after injection. A clear signal was obtained in the inguinal LN, draining lymphatics, and axillary LN at 4 h, and it was still detectable at 48 h. Control Alexa488-IgG showed minimal signal in the draining lymphatics at 4 h after injection and no signal at 12 h after injection. Immunostaining of lymphatic tissue showed that Alexa488-anti-LYVE-1 was localized to lymphatic endothelium, whereas no signal was observed in the adjacent arteries and veins. Human XPA-1 pancreatic cancer cells transfected with red fluorescent protein (2 × 106 cells) were injected into the tissue around the mammary inguinal LN in nude mice (n = 6) 4 h after injection of Alexa488-anti-LYVE-1. The tumor cells expressing the red fluorescent protein were clearly visible within the lymphatic vessels trafficking from the inguinal LN to the axillary LN in all six mice.

Other Non-Primate Mammals

[PubMed]

No publication is currently available.

Non-Human Primates

[PubMed]

No publication is currently available.

Human Studies

[PubMed]

No publication is currently available.

NIH Support

CA099258, CA103563, R01, CA109949-01

References

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Clement O., Luciani A. Imaging the lymphatic system: possibilities and clinical applications. Eur Radiol. 2004;14(8):1498–507. [PubMed: 15007613]
2.
Styblo T., Aarsvold J.N., Grant S.F., Cohen C., Larsen T., Waldrop S., Alazraki N.P. Sentinel lymph nodes: optimizing success. Semin Roentgenol. 2001;36(3):261–9. [PubMed: 11475072]
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Hoh C.K., Wallace A.M., Vera D.R. Preclinical studies of [(99m)Tc]DTPA-mannosyl-dextran. Nucl Med Biol. 2003;30(5):457–64. [PubMed: 12831982]
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Salem C.E., Hoh C.K., Wallace A.M., Vera D.R. A preclinical study of prostate sentinel lymph node mapping with [99mTC]diethylenetetramine pentaacetic acid-mannosyl-dextran. J Urol. 2006;175(2):744–8. [PubMed: 16407043]
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Vera D.R., Wallace A.M., Hoh C.K., Mattrey R.F. A synthetic macromolecule for sentinel node detection: (99m)Tc-DTPA-mannosyl-dextran. J Nucl Med. 2001;42(6):951–9. [PubMed: 11390562]
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Torabi M., Aquino S.L., Harisinghani M.G. Current concepts in lymph node imaging. J Nucl Med. 2004;45(9):1509–18. [PubMed: 15347718]
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Luciani A., Itti E., Rahmouni A., Meignan M., Clement O. Lymph node imaging: basic principles. Eur J Radiol. 2006;58(3):338–44. [PubMed: 16473489]
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Wunderbaldinger P. Problems and prospects of modern lymph node imaging. Eur J Radiol. 2006;58(3):325–37. [PubMed: 16464553]
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Qian C.N., Berghuis B., Tsarfaty G., Bruch M., Kort E.J., Ditlev J., Tsarfaty I., Hudson E., Jackson D.G., Petillo D., Chen J., Resau J.H., Teh B.T. Preparing the "soil": the primary tumor induces vasculature reorganization in the sentinel lymph node before the arrival of metastatic cancer cells. Cancer Res. 2006;66(21):10365–76. [PubMed: 17062557]
11.
Harrell M.I., Iritani B.M., Ruddell A. Tumor-induced sentinel lymph node lymphangiogenesis and increased lymph flow precede melanoma metastasis. Am J Pathol. 2007;170(2):774–86. [PMC free article: PMC1851877] [PubMed: 17255343]
12.
Dadras S.S., Lange-Asschenfeldt B., Velasco P., Nguyen L., Vora A., Muzikansky A., Jahnke K., Hauschild A., Hirakawa S., Mihm M.C., Detmar M. Tumor lymphangiogenesis predicts melanoma metastasis to sentinel lymph nodes. Mod Pathol. 2005;18(9):1232–42. [PubMed: 15803182]
13.
Van den Eynden G.G., Vandenberghe M.K., van Dam P.J., Colpaert C.G., van Dam P., Dirix L.Y., Vermeulen P.B., Van Marck E.A. Increased sentinel lymph node lymphangiogenesis is associated with nonsentinel axillary lymph node involvement in breast cancer patients with a positive sentinel node. Clin Cancer Res. 2007;13(18 Pt 1):5391–7. [PubMed: 17875768]
14.
Jiang D., Liang J., Noble P.W. Hyaluronan as an immune regulator in human diseases. Physiol Rev. 2011;91(1):221–64. [PMC free article: PMC3051404] [PubMed: 21248167]
15.
Sironen R.K., Tammi M., Tammi R., Auvinen P.K., Anttila M., Kosma V.M. Hyaluronan in human malignancies. Exp Cell Res. 2011;317(4):383–91. [PubMed: 21134368]
16.
Aruffo A., Stamenkovic I., Melnick M., Underhill C.B., Seed B. CD44 is the principal cell surface receptor for hyaluronate. Cell. 1990;61(7):1303–13. [PubMed: 1694723]
17.
McElroy M., Hayashi K., Garmy-Susini B., Kaushal S., Varner J.A., Moossa A.R., Hoffman R.M., Bouvet M. Fluorescent LYVE-1 antibody to image dynamically lymphatic trafficking of cancer cells in vivo. J Surg Res. 2009;151(1):68–73. [PMC free article: PMC2628480] [PubMed: 18599080]

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