Soluble recombinant human podoplanin receptor

Abstract

This article discloses a material composition and a method for using the composition to treat... For example Methods for treating cancer or inflammatory joint diseases. The composition is a soluble recombinant human flatfoot protein receptor (srhPDPN) comprising a first amino acid sequence at least 95% homologous to SEQ ID NO:1. The srhPDPN may comprise a tag peptide or polypeptide (such as a multihistidine tag) fused to the first amino acid sequence. The srhPDPN may comprise a signal peptide fused to the first amino acid sequence. The signal peptide may comprise an amino acid sequence at least 95% homologous to SEQ ID NO:2. Multiple threonine residues of the srhPDPN may be partially glycosylated with sialic acid, and in some embodiments, 17 threonine residues of the srhPDPN are partially glycosylated with sialic acid. Treatment may include allowing the composition to act as a decoy receptor or ligand trap to inhibit PDPN signaling.

Description

Cross-references to related applications

[0001] This application claims priority to U.S. Provisional Patent Application No. 63 / 537,975, filed September 12, 2023, the contents of which are incorporated herein by reference in their entirety.

[0002] Declaration of sequence list This application contains a sequence list electronically submitted in ST.26 XML file format, created on August 22, 2024, named SENTRI002_SL.xml, and measuring 3,534 bytes. This ST.26 XML file is incorporated herein by reference in its entirety. Technical Field

[0003] This disclosure relates to the PDPN receptor, and more specifically, to the soluble recombinant human PDPN receptor and its uses. Background Technology

[0004] This section aims to introduce the reader to various aspects of the technology that may relate to the aspects of the invention described below and / or claimed. This discussion is intended to help provide the reader with background information to facilitate a better understanding of the various aspects of the invention. Therefore, it should be understood that these statements should be read in this context and not as an endorsement of prior art.

[0005] The podoplanin (PDPN) receptor has been identified as a biologically relevant target. Regulation of PDPN can... For example It inhibits the growth and motility of human cancer cells. Summary of the Invention

[0006] The following addresses various deficiencies in the prior art through the disclosed material compositions and techniques.

[0007] In various aspects, a composition of matter may be provided. The composition of matter may comprise a soluble recombinant human flatfoot protein receptor (srhPDPN) comprising a first amino acid sequence at least 95% homologous to SEQ ID NO:1, and a tag peptide or polypeptide, such as a multihistidine tag, fused to the first amino acid sequence. The srhPDPN may comprise a signal peptide fused to the first amino acid sequence. The signal peptide may comprise, for example, an amino acid sequence at least 95% homologous to SEQ ID NO:2. Multiple threonine residues (such as at least 15) of the first amino acid sequence may be partially glycosylated with sialic acid. In some aspects, 17 threonine residues of the first amino acid sequence are partially glycosylated with sialic acid.

[0008] In all respects, cell lines containing genes encoding material compositions as disclosed herein can be provided. These cell lines can be human cell lines.

[0009] In various aspects, a pharmaceutical composition may be provided. The composition may comprise a composition of substances as disclosed herein, as well as a pharmaceutically acceptable carrier. The pharmaceutical composition may also comprise, for example, flavor additives, lubricants, binders, preservatives, encapsulating materials, diluents, artificial colorants, flavor additives, binders, stabilizers, natural or artificial sweeteners, thickeners, tablet disintegrants, magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, hardening agents, gelatin, tragacanth gum, methylcellulose, and / or sodium carboxymethyl cellulose.

[0010] In various aspects, a method for treating cancer or inflammatory joint diseases may be provided. The method may include providing an effective amount of the material composition according to claim 1. The method may include allowing the material composition to act as a decoy receptor or ligand trap to inhibit PDPN signaling. Cancer may be, for example, carcinoma, leukemia, lung cancer, colon cancer, central nervous system (CNS) cancer, melanoma, ovarian cancer, kidney cancer, prostate cancer, and / or breast cancer. Inflammatory joint diseases may be arthritis, such as osteoarthritis or rheumatoid arthritis.

[0011] In various aspects, a method for inhibiting the expression of Pdpn on cells can be provided. This method may include providing a cell culture comprising tumor cells and / or normal cells. This method may include subjecting tumor cells to a sufficient amount of a material composition as disclosed herein. This method may include allowing the material composition to act as a decoy receptor or ligand trap to inhibit PDPN signaling. Attached Figure Description

[0012] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and, together with the general description of the invention given above and the detailed description of the embodiments given below, serve to explain the principles of the invention.

[0013] Figure 1 This is a schematic diagram of an example of a synthetic recombinant human PDPN (srhPDPN) sequence.

[0014] Figure 2 The image shows the results of SDS-PAGE, where shrPDPN (5 ug / lane) was resolved by reverting to 12% SDS-PAGE and visualized by staining with the molecular weight markers shown.

[0015] Figure 3This is a graph illustrating cell migration after 24 hours of treatment with 0 nM, 770 nM, 1440 nM, or 2880 nM srhPDPN, assessed by a wound healing assay. Data were normalized and displayed as a percentage of the untreated control (mean + SEM, n=2), where single asterisks, double asterisks, and triple asterisks represent p<0.05, p<0.01, and p<0.001, respectively, as indicated by the test.

[0016] Figure 4 This graph illustrates the viability of cells treated with 0 nM, 770 nM, 1440 nM, or 2880 nM srhPDPN for 24 hours, assessed by AlamarBlue assay. Data were normalized and displayed as a percentage of the untreated control (mean + SEM, n=2). Double, triple, and quadruple asterisks indicate p<0.01, p<0.001, and p<0.0001, respectively, as indicated by the test.

[0017] It should be understood that the accompanying drawings are not necessarily drawn to scale and present slightly simplified representations of various features illustrating the basic principles of the invention. Specific design features such as the sequence of operations disclosed herein, including, for example, the specific dimensions, orientations, positions, and shapes of the various illustrated components, will be determined to some extent by the specific intended application and usage environment. Some features of the illustrated embodiments have been enlarged or distorted relative to other features to facilitate visual display and clear understanding. Specifically, thin features may be thickened, for example, for clarity or illustrative purposes. Detailed Implementation

[0018] The following description and accompanying drawings illustrate only the principles of the invention. It will therefore be understood that those skilled in the art will be able to design various arrangements, which, while not explicitly described or shown herein, embody the principles of the invention and are included within its scope. Furthermore, all embodiments detailed herein are primarily intended for illustrative purposes only to aid the reader in understanding the principles of the invention and the concepts contributed by the inventors to advance the technology, and should be understood as not being limited to such specifically detailed embodiments and conditions. Additionally, as used herein, the term "or" means non-exclusive or unless otherwise specified ( For example (Otherwise, or in an alternative). Moreover, the various embodiments described herein are not necessarily mutually exclusive, as some embodiments can be combined with one or more other embodiments to form new embodiments.

[0019] The numerous innovative teachings of this application will be described with particular reference to the presently preferred exemplary embodiments. However, it should be understood that such embodiments provide only a few examples of the many advantageous uses of the innovative teachings herein. Generally, the statements in this specification do not necessarily limit any of the various claimed inventions. Furthermore, some statements may apply to some inventive features but not to others. Those skilled in the art and affected by the teachings herein will recognize that the invention is also applicable to a variety of other technical fields or embodiments.

[0020] In various aspects, a material composition may be provided. This material composition may comprise a soluble recombinant human flatfoot protein receptor (srhPDPN).

[0021] refer to Figure 1 srhPDPN (100) may contain a first amino acid sequence (110). The first amino acid sequence may contain at least a portion of human PDPN. In some embodiments, this may contain amino acids 23-132 of human PDPN: ASTGQPEDDT ETTGLEGGVA MPGAEDDVVT PGTSEDRYKS GLTTLVATSV NSVTGIRIEDLPTSESTVHA QEQSPSATAS NVATSHSTEK VDGDTQTTVE KDGLSTVTLV (SEQ ID NO:1) In some embodiments, the first amino acid sequence may be a variant having at least 99% homology with SEQ ID NO:1. In some embodiments, the first amino acid sequence may be a variant having at least 98% homology with SEQ ID NO:1. In some embodiments, the first amino acid sequence may be a variant having at least 97% homology with SEQ ID NO:1. In some embodiments, the first amino acid sequence may be a variant having at least 96% homology with SEQ ID NO:1. In some embodiments, the first amino acid sequence may be a variant having at least 95% homology with SEQ ID NO:1. "Variant" is intended to mean substantially similar sequences. For nucleic acid molecules, variants comprise nucleic acid molecules having: deletions (i.e., truncation) at the 5' and / or 3' ends; deletions and / or additions of one or more nucleotides at one or more internal sites of a native polynucleotide; and / or substitutions of one or more nucleotides at one or more sites of a native polynucleotide. In a preferred embodiment, the threonine residue in SEQ ID NO:1 is not deleted or substituted. In a preferred embodiment, the threonine residue in SEQ ID NO:1 is not deleted or substituted. In some embodiments, neither the serine nor the threonine residues in SEQ ID NO:1 are deleted or substituted.

[0022] In various respects, serine and threonine residues can be glycosylation sites of the first amino acid sequence.

[0023] In various aspects, one or more threonine residues of the first amino acid sequence may be partially glycosylated with sialic acid. In a preferred embodiment, multiple threonine residues of the first amino acid sequence may be partially glycosylated with sialic acid. In some embodiments, this may include at least 5, at least 10, or at least 15 threonine residues of the first amino acid sequence being partially glycosylated with sialic acid. In some embodiments, 17 threonine residues of the first amino acid sequence are partially glycosylated with sialic acid. In some embodiments, at least one threonine residue of the first amino acid sequence is not glycosylated.

[0024] In some embodiments, at least one serine residue of the first amino acid sequence is glycosylated. In some embodiments, multiple serine residues are glycosylated. In some embodiments, eight serine residues are glycosylated. In some embodiments, at least one serine residue is not glycosylated. In some embodiments, at least one serine residue is not glycosylated.

[0025] srhPDPN can contain a second amino acid sequence, such as a tag peptide or polypeptide fused to the first amino acid sequence. (Reference) Figure 1 srhPDPN (100) may contain a tag peptide or polypeptide (120) fused to the first amino acid sequence.

[0026] Tagned peptides or polypeptides may include affinity tags (e.g., peptides or polypeptides that bind to certain agents or matrices), solubilizing tags (e.g., peptides or polypeptides that help proteins fold correctly and prevent precipitation), chromatographic tags (e.g., peptides or polypeptides that modify the chromatographic properties of proteins to provide different resolutions in a particular separation technique), epitope tags (e.g., peptides or polypeptides that bind to antibodies), fluorescent tags (e.g., peptides or polypeptides that fluoresce when exposed to light of a predetermined wavelength), or self-cleaving tags (e.g., peptides or polypeptides that have inducible proteolytic activity, such as sorting enzyme tags, Npro tags, FrpC modules, CPDs) or combinations thereof.

[0027] Non-limiting examples of affinity tags include maltose-binding protein (MBP) tags, glutathione S-transferase (GST) tags, His tags, SBP tags, Strep tags, and calmodulin tags. Non-limiting examples of solubility tags include thioredoxin (TRX) tags, NANP tags, MBP tags, SUMO tags, GB1 tags, NUSA CBD tags, and GST tags. Non-limiting examples of chromatographic tags include polyanionic amino acid tags (e.g., FLAG tags) and polyglutamic acid tags. Non-limiting examples of epitope tags include V5 tags, VSV tags, E tags, NE tags, hemagglutinin (Ha) tags, Myc tags, and FLAG tags. Non-limiting examples of fluorescence tags include green fluorescent protein (GFP) tags, blue fluorescent protein (BFP) tags, cyan fluorescent protein (CFP) tags, yellow fluorescent protein (YFP) tags, orange fluorescent protein (OFP) tags, red fluorescent protein (RFP) tags, and derivatives thereof. In some embodiments, a multihistidine affinity tag, such as DHHHHHH ([SEQ ID NO: 3]), may be used.

[0028] In some embodiments, the second amino acid sequence may be fused to the first end (such as the C-terminus) of the first amino acid sequence.

[0029] srhPDPN may contain a third amino acid sequence (such as a signal peptide or polypeptide) fused to the first amino acid sequence. (Reference) Figure 1 srhPDPN (100) may contain a signal peptide or polypeptide (130) fused to a first amino acid sequence. srhPDPN (100) may contain a tag peptide or polypeptide (120) fused to a first amino acid sequence and a signal peptide or polypeptide (130).

[0030] In some embodiments, the signal peptide may be a 19-amino acid signal peptide derived from the mouse Ig heavy chain V region BCL1: MGWSCIIFFLVATATGVHS (SEQ ID NO:2). However, other suitable signal peptides may be used.

[0031] In some embodiments, the third amino acid sequence may be a variant having at least 94% homology with SEQ ID NO:3 (e.g., including single nucleotide deletions / substitutions / additions). In some embodiments, the third amino acid sequence may be a variant having at least 89% homology with SEQ ID NO:3 (e.g., including no more than two nucleotide deletions / substitutions / additions).

[0032] The third amino acid sequence may be fused to the end of the first amino acid sequence opposite to the second amino acid sequence. In some embodiments, the third amino acid sequence may be fused to the second end (such as the N-terminus) of the first amino acid sequence.

[0033] In some embodiments, a pharmaceutical composition may be provided. The composition may comprise examples of srhPDPN as disclosed herein, as well as a pharmaceutically acceptable carrier. The term “pharmaceutically acceptable carrier” includes any and all solvents, dispersion media, coatings, antimicrobial and antifungal agents, isotonic agents, and absorption delay agents, etc. The use of such media and agents for the active pharmaceutical ingredient is well known in the art. Their use in a therapeutic composition is considered unless any conventional media or agent is incompatible with the active ingredient. Additionally, various adjuvants, such as those commonly used in the art, may be included. Considerations for including various components in a pharmaceutical composition are described, for example, in Gilman et al. (ed.) (1990); Goodman and Gilman, The Pharmacological Basis of Therapeutics, 8th ed., Pergamon Press, which is incorporated herein by reference in its entirety.

[0034] In some embodiments, the pharmaceutical composition may comprise flavor additives, lubricants, binders, preservatives, encapsulating materials, diluents, artificial colorants, flavor additives, binders, stabilizers, natural or artificial sweeteners, thickeners, tablet disintegrants, magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, hardening agents, gelatin, tragacanth gum, methylcellulose and / or sodium carboxymethylcellulose.

[0035] In various aspects, a cell line may be provided. The cell line may comprise one or more cells containing a gene encoding an embodiment of the disclosed srhPDPN. In some embodiments, the cell line may be a human cell line.

[0036] In various aspects, it can provide a treatment for cancers (such as carcinoma, leukemia, lung cancer, colon cancer, central nervous system (CNS) cancers, melanoma, ovarian cancer, kidney cancer, prostate cancer, and / or breast cancer) or inflammatory joint diseases ( example like Methods for treating arthritis, such as osteoarthritis or rheumatoid arthritis. The method may include providing an effective amount of the disclosed srhPDPN. The method may include allowing the srhPDPN to act as a decoy receptor or ligand trap to inhibit PDPN signaling.

[0037] In some embodiments, the effective concentration of srhPDPN in the fluid surrounding cancer cells can be in the range of about 10 nM to about 5000 nM, such as about 50 nM to about 2000 nM. In some embodiments, the effective amount of srhPDPN can be in the range of about 1 µg / kg body weight to about 1 mg / kg body weight, which can be readily determined by taking into account the route of administration, the time of administration of the lectin, and other factors known to those skilled in the art.

[0038] In various aspects, a method for inhibiting Pdpn expression on cells can be provided. This method may include providing a cell culture comprising tumor cells and / or normal cells. This method may include subjecting the cells to a disclosed srhPDPN. This method may include allowing srhPDPN to act as a decoy receptor or ligand trap to inhibit PDPN signaling.

[0039] The total concentration of srhPDPN in the fluid surrounding cancer cells can range from about 10 nM to about 5000 nM, such as about 50 nM to about 2000 nM.

[0040] Mountain locust (Maackia amurensis) Lectins have been used in research for over 60 years. In particular, Mountain locust Seed lectin (MASL) has been used as an agent that binds to α-2-3-linked sialic acid. These glycosylation modifications are commonly found on extracellular protein receptors associated with viral infection, inflammation, and cancer. Therefore, MASL can target these receptors to inhibit viral infection, arthritis development, and cancer progression. For example, MASL inhibits the binding of the SARS-CoV-2 spike protein to the ACE2 receptor in cell cultures. MASL also targets the PDPN receptor to inhibit the progression of osteoarthritis and rheumatoid arthritis in mice and to inhibit excessive proliferation of psoriatic epidermis in skin cultures. In addition, MASL targets the PDPN receptor to inhibit the motility and viability of melanoma cells in cultures and tumor progression in mice. MASL also targets the PDPN receptor to inhibit the growth and motility of oral squamous cell carcinoma (OSCC) cells and is being evaluated as a treatment for oral cancer in an ongoing Phase 1 human clinical trial (NCT04188665). Mountain locust Lectins can also target receptors to inhibit the viability of non-small cell lung cancer and childhood acute lymphoblastic leukemia cells.

[0041] The PDPN receptor has been identified as a biologically relevant MASL target. It is hypothesized that sialic acid on PDPN is involved in MASL binding. Soluble recombinant human PDPN (srhPDPN) was generated in human HEK293F cells to verify the sialic acid modification of this receptor.

[0042] Specifically, the sequence encoding a protein consisting of a 19-amino acid signal peptide (SEQ ID NO:2) from the V region of the mouse Ig heavy chain BCL1, followed by the entire extracellular region of human PDPN amino acids 23-132 (SEQ ID NO:1) terminated by an HIS tag (SEQ ID NO:3), was engineered into pcDNA3.1(+) and transfected into FREESTYLE™ HEK293F cells (ThermoFisher #R790-07). After tangential percolation of the culture medium, the resulting soluble recombinant human PDPN (srhPDPN) was purified on a Ni agarose gel, then exchanged for PBS on a SUPERDEX™ 200 increase column, and analyzed by SDS-PAGE. For mass spectrometry analysis, srhPDPN (0.5 µg / µl, dissolved in 25 mM ammonium bicarbonate, pH 8) was digested with trypsin (0.01 µg / µl) or GluC (0.01 µg / µl) (sequencing grade; Promega) at 37°C for 16 h. The digestion reaction was terminated by adding trifluoroacetic acid to 1%. The peptide mixture (10 µl) was injected and analyzed by LC-MS / MS on a DIONEX™ ULTIMATE™ 3000 RSLCnano system connected in-line to a Q EXTRACTIVE™ HFBiopharma mass spectrometer (Thermo). The sample was collected for 2 min at a rate of 20 μl / min in loading solvent A (0.1% aqueous trifluoroacetic acid) on a 5 mm trapping column (Thermo Scientific, 300 μm inner diameter (ID), 5 μm beads). Peptides were separated on a 250 mm Aurora Ultimate, 1.7 µm C18, 75 µm inner diameter (IonOpticks) spectrometer maintained at a constant temperature of 45 °C. The peptides were eluted via a nonlinear gradient, starting with 0.5% Solvent B, reaching 26% Solvent B (0.1% trifluoroacetic acid in acetonitrile) within 30 min, 44% Solvent B within 38 min, followed by washing with 56% Solvent B for 7 min, and reequilibration with Solvent A at a flow rate of 300 nl / min. The mass spectrometer was operated in data correlation mode, automatically switching between MS and MS / MS acquisition to acquire the 12 most abundant ion peaks for each MS spectrum. After accumulating to a target value of 3,000,000, full-scan MS spectra (375–1500 m / z) were acquired at a resolution of 60,000 in an Orbitrap analyzer. After filling the trap with a target value of 100,000 for a maximum of 120 ms, the 12 strongest ions above the threshold of 15,000 are separated with a width of 1.5 m / z and fragmented with 28% of the normalized collision energy.MS / MS spectra (200–2000 m / z) were obtained at a resolution of 15,000 in an Orbitrap analyzer. During the project, a polydimethylcyclosiloxane background ion of 445.120028 Da was used for internal calibration (locking in quality), and QCloud was used to control longitudinal instrument performance. Data analysis was performed using the peptide mapping tool with BioPharma Finder software (Thermo Fisher Scientific). The obtained MS / MS spectra were analyzed using BioPharma Finder 3.0 software (Thermo Fisher Scientific), and the selected trypsin or Glu-C was mapped to the appropriate protein sequence. For peptide identification, the following parameters were used: a maximum peptide quality of 7000 Da, a quality accuracy of 5 ppm, and a minimum confidence level of 0.80. Deamidation of asparagine and glutamine, and oxidation of methionine and tryptophan were set as variable modifications. Searching for glycosylation modifications (human-specific) was implemented, and the maximum number of variable modifications per peptide was set to 2.

[0043] like Figure 2 As shown, the protein migrated by SDS-PAGE with an estimated molecular weight of 24.6 kD instead of its expected size of 12 kD.

[0044] Sequencing of the protein by LC-MS / MS revealed that PDPN was glycosylated at 26 amino acids. These glycosylation events occurred only at serine or threonine residues. Seventeen of these 26 modifications contained sialic acid, including threonine glycosylation at residues 34 and 52, as previously reported.

[0045] Soluble receptors can act as "ligand traps" to inhibit oncogenic signaling. To demonstrate the potential of srhPDPN to inhibit oncogenic PDPN signaling, tests were conducted on human oral squamous cell carcinoma (OSCC) cells exposed to srhPDPN.

[0046] Specifically, Sen1bs human OSCC cells were obtained from oral cancer patients participating in a clinical trial (#NCT04188665). They were maintained at 37°C with 5% CO2 and 100% humidity in DMEM (Hyclone SH30021) supplemented with 25 mM HEPES (Hyclone SH30237) and FBS (Seradigm 1400–500), and grown to confluence on 6-well tissue culture cluster plates (Falcon 353224) as described. For migration assays, cell monolayers were scraped immediately before and 24 hours after treatment with shPDPN at 0 nM, 770 nM, 1440 nM, and 2280 nM, and observed from 24 to 48 hours post-treatment. Migration was quantified based on the number of cells entering a 123 × 123 μm square placed along the center of the wound. Sister plates treated with shPDPN for 48 hours were incubated with alamarBlue (BioRad #BUF012A) for 4 hours and assayed (excitation / emission: 570 / 600 nm) to assess cell viability as a metabolic activity by measuring the reduction of rezazon dye to halogen, as known in the art. All assays were run at least 3 times, and the results were similar.

[0047] srhPDPN inhibits cell motility and viability in a dose-dependent manner, consistent with its potential to act as a PDPN ligand trap. Compared with untreated controls, srhPDPN reduced cell motility by 36% ± 6.5%, 63% ± 12%, and 39% ± 1.4% at 770 nM, 1540 nM, and 3080 nM, respectively (mean ± SEM, n = 2). Figure 3 As shown. Compared with the untreated control, srhPDPN also reduced cell viability by 47%±2.5%, 61%±1.5%, and 70%±3.0% at 770 nM, 1540 nM, and 3080 nM, respectively. Figure 4 As shown.

Claims

1. A composition comprising: Soluble recombinant human flatfoot protein receptor (srhPDPN), comprising: The first amino acid sequence that is at least 95% homologous to SEQ ID NO:1; and A tag peptide or polypeptide fused to the first amino acid sequence.

2. The composition of claim 1, wherein the tagged peptide or polypeptide comprises a multihistidine tag.

3. The composition of claim 1, wherein the srhPDPN further comprises a signal peptide or polypeptide fused to the first amino acid sequence.

4. The composition of claim 3, wherein the signal peptide or polypeptide comprises an amino acid sequence that is at least 95% homologous to SEQ ID NO:

2.

5. The composition according to claim 1, wherein a plurality of threonine residues of the first amino acid sequence are partially glycosylated with sialic acid.

6. The composition of claim 5, wherein at least 15 threonine residues of the first amino acid sequence are partially glycosylated with sialic acid.

7. The composition of claim 6, wherein 17 threonine residues of the first amino acid sequence are partially glycosylated with sialic acid.

8. A cell line comprising a gene encoding the composition of the substance according to claim 1.

9. The cell line of claim 8, wherein the cell line is a human cell line.

10. A pharmaceutical composition comprising: The material composition according to claim 1; and Pharmaceutically acceptable carrier.

11. The pharmaceutical composition of claim 10, further comprising flavor additives, lubricants, binders, preservatives, encapsulating materials, diluents, artificial colorants, flavor additives, binders, stabilizers, natural or artificial sweeteners, thickeners, tablet disintegrants, magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, hardening agents, gelatin, tragacanth gum, methylcellulose and / or sodium carboxymethyl cellulose.

12. A method for treating cancer or inflammatory joint diseases, comprising: Provide an effective amount of the material composition according to claim 1; as well as The material composition is allowed to act as a decoy receptor or ligand trap to inhibit PDPN signaling.

13. The method of claim 12, wherein the cancer is cancer, leukemia, lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, kidney cancer, prostate cancer, and / or breast cancer.

14. The method of claim 12, wherein the inflammatory joint disease is arthritis.

15. The method of claim 14, wherein the arthritis is osteoarthritis or rheumatoid arthritis.

16. A method for inhibiting the expression of Pdpn on cells, comprising: Provide cell cultures containing tumor cells and / or normal cells; The tumor cells are subjected to a sufficient amount of the composition according to claim 1; as well as The material composition is allowed to act as a decoy receptor or ligand trap to inhibit PDPN signaling.

Images