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Duffy antigen receptor for chemokines and use thereof

A chemokine receptor and chemokine technology, applied in the fields of application, antibody, anti-receptor/cell surface antigen/cell surface determinant immunoglobulin, etc., can solve the problem that the exact function of DARC and tumor-associated blood vessels have not been reported problems such as reduction

Inactive Publication Date: 2007-10-31
NEW YORK BLOOD CENT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0012] The references described above, highlighting the role of DARC in angiogenesis, Debsaillets et al. reported the need for further in vivo studies; Gershengorn did not report the precise function of DARC, and Addison et al. reported that tumors expressing DARC exhibit tumor-associated angiogenesis. reduce

Method used

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  • Duffy antigen receptor for chemokines and use thereof
  • Duffy antigen receptor for chemokines and use thereof
  • Duffy antigen receptor for chemokines and use thereof

Examples

Experimental program
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Embodiment 1

[0109] Example 1: Materials and methods

[0110] Mouse Strains: The construction of Duffy knockout (DKO) mice has been described previously (Luo et al., Genome Research 1997, 7:932-941). Hybrid knockout mice [Dfy(+ / -)] were crossed to generate Dfy(+ / +) and Dfy(- / -) purebred congeners. Experiments were performed with age and sex matched animals. C57BL / 6J mice were purchased from Jackson Laboratory (Bar Harbor, ME).

[0111] Tumor formation: Lewis lung carcinoma (LLC) cells were grown in logarithmic phase, harvested and grown at 1×10 7 cells / ml were suspended in PBS. 100 [mu]l of the cell suspension was injected subcutaneously near the midline of the back of each animal (n=5). Fourteen days after injection, tumor growth and necrosis in each group of mice were monitored. After sacrifice of the mice, tumor size was digitally photographed and the entire tumor growth was weighed.

[0112] Histochemistry: For evaluation of necrosis and angiogenesis, tumors were fixed in 10% pho...

Embodiment 2

[0114] Example 2: Tumor Growth in Tamiflu Wild-Type and Tamiflu Knockout Mice

[0115] Solid tumors in Dfy(+ / +) (wild type, WT) and Dfy(- / -) (Duffy knockout, DKO) mice were formed by injection of Lewis lung carcinoma (LLC) cells. Tumors began to grow at the same rate in wild-type and knockout mice. Interestingly, tumors in the knockout mice began to show signs of necrosis earlier than in wild-type mice.

[0116] After 14 days, mice were sacrificed. Tumors were removed, weighed and compared. The results showed that solid tumors grew more slowly (by size and weight) in DARC knockout mice compared to wild-type mice (Figure 1).

[0117] Tumors in knockout mice experienced severe necrosis (see arrows in Figure 2a), whereas no necrosis was observed in tumors in wild-type mice (Figure 2a). Tumors in Dfy knockout mice had more necrosis and vessel rupture compared to Dfy(+ / +) mice (Fig. 2b). Furthermore, immunohistological studies showed that there was less microcapillary formatio...

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Abstract

The invention relates to Duffy antigen receptor for chemokines and uses thereof. In on embodiment, the invention provides a method for screening for drug candidates that inhibit angiogenesis. The method comprises contacting a molecule with a Duffy antigen receptor for chemokines and determining whether the molecule binds to the Duffy antigen receptor for chemokines. In another embodiment, the invention provides a method for inhibiting tumor growth. In yet another embodiment, the invention provides a method for inhibiting angiogenesis. In a further embodiment, the invention provides a method for promoting tumor necrosis.

Description

technical field [0001] This application claims priority to US Provisional Application Serial No. 60 / 620,993, filed October 21, 2004, the entire specification of which is hereby incorporated by reference herein. Background technique [0002] Duffy blood group protein is a member of the seven transmembrane domain chemokine receptor family (Chaudhuri et al., PNAS, 1993, 90: 10793-10797). This protein is capable of binding chemokines such as CXC and CC chemokines. Therefore, this protein is also called Duffy Antigen Chemokine Receptor (DARC) (Chaudhuri et al., J Biol Chem. 1994, 269: 7835-7838 and Horuk el al., Immunol Today 1994, 15: 169- 174). [0003] In addition to being expressed on erythrocytes, DARC is also present on endothelial cells. For example, DARC is present on microvascular endothelial cells of various nonerythroid organs such as liver, lung, thyroid, and spleen; also on epithelial cells of lung and renal collecting ducts (Chaudhuri et al., Blood 1997, 89 :701...

Claims

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Application Information

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IPC IPC(8): A61K8/18C12N15/00A61Q13/00C12N5/18C07H21/04C12P21/00
CPCC07K16/2866G01N2500/00A61K2039/505C07K2317/73G01N33/6863C07K16/30A61P35/00A61K39/395G01N33/567
Inventor 阿索克·乔杜里
Owner NEW YORK BLOOD CENT
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