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WO2006061430A2 - Itgbl-1 utile comme cible regulant la metastase osseuse et le developpement osseux - Google Patents

Itgbl-1 utile comme cible regulant la metastase osseuse et le developpement osseux Download PDF

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Publication number
WO2006061430A2
WO2006061430A2 PCT/EP2005/056636 EP2005056636W WO2006061430A2 WO 2006061430 A2 WO2006061430 A2 WO 2006061430A2 EP 2005056636 W EP2005056636 W EP 2005056636W WO 2006061430 A2 WO2006061430 A2 WO 2006061430A2
Authority
WO
WIPO (PCT)
Prior art keywords
bone
bone metastasis
gene
marker
itgbl1
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/EP2005/056636
Other languages
English (en)
Other versions
WO2006061430A3 (fr
Inventor
Philippe Clement-Lacroix
Philippe Clezardin
Amanda Jackson
Philippe Pujuguet
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Institut National de la Sante et de la Recherche Medicale INSERM
Galapagos SAS
Original Assignee
Institut National de la Sante et de la Recherche Medicale INSERM
ProSkelia SAS
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Institut National de la Sante et de la Recherche Medicale INSERM, ProSkelia SAS filed Critical Institut National de la Sante et de la Recherche Medicale INSERM
Publication of WO2006061430A2 publication Critical patent/WO2006061430A2/fr
Publication of WO2006061430A3 publication Critical patent/WO2006061430A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/136—Screening for pharmacological compounds
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/158—Expression markers

Definitions

  • ITGBL1 appears to be a target relevant to the homing of breast cancer cells to bone and during bone development.
  • Some genes have been identified whose regulated expression is involved in the establishment of bone metastasis (5, 6). At least four key cellular functions are now causally involved in bone metastasis: homing, invasion, angiogenesis and osteolysis regulated respectively through CXCR4, MMP1 , CTGF/FGF5 and IL11/OPN (4). However, an incomplete understanding of the cellular and molecular mechanisms underlying bone metastasis hinders the development of effective therapies that would eliminate or ameliorate this condition (11 ).
  • bone disorders encompass any disorders of bone metabolism, including without any limitation bone metastases (which may be seen as excessive bone developments) and bone defects (regarded as insufficient bone developments).
  • the monoclonal antibody is incubated in the dish during which time the monoclonal antibodies attach to the specific marker polypeptide attached to the polystyrene dish. All unbound monoclonal antibody is washed out with buffer.
  • the reporter antibody linked to horseradish peroxidase is now placed in the dish resulting in binding of the reporter antibody to any monoclonal antibody bound to the specific marker polypeptide. Unattached reporter antibody is then washed out.
  • Peroxidase substrates are then added to the dish and the amount of color developed in a given time period is a measurement of the amount of the specific marker polypeptide present in a given volume of patient sample when compared against a standard curve.
  • methods for detecting an inhibition or an enhancement of the biological activity of a marker such as ITGBL1 include both in vitro and in vivo procedures (e.g., protein-protein binding assays, biochemical screening assays, immunoassays, cell-based assays, animal model experiments, which are well-characterized in the art).
  • in vitro and in vivo procedures e.g., protein-protein binding assays, biochemical screening assays, immunoassays, cell-based assays, animal model experiments, which are well-characterized in the art.
  • the person skilled in the art may use only one in vitro and/or one in vivo selection technique. However, in order to strengthen the validity and reproducibility of the results, this person may prefer to use at least two in vitro and/or at least two in vivo selection methods. Examples of in vitro and in vivo procedures for showing an inhibitory or an enhancer activity on ITGBL1 are described below.
  • the present invention discloses methods for selecting a therapeutic which forms a complex with bone metastasis specific proteins with sufficient affinity to prevent their biological action.
  • the methods include various assays, including competitive assays where the proteins are immobilized to a support, and are contacted with a natural substrate and a labeled therapeutic candidate, either simultaneously or in either consecutive order, and determining whether the therapeutic candidate effectively competes with the natural substrate in a manner sufficient to prevent binding of the protein to its substrate.
  • a DNA oligonucleotide is designed to be complementary to a region of the gene involved in transcription, thereby preventing transcription and the production of a bone metastasis specific polynucleotide.
  • the antisense RNA oligonucleotide hybridizes to the mRNA in vivo and blocks translation of the mRNA molecule into the corresponding specific marker polypeptide;
  • the oligonucleotides can also be delivered to cells such that the antisense RNA or DNA may be expressed in vivo to inhibit production of the specific marker polypeptides.
  • Another example is a small molecule which binds to and occupies the active site of the specific marker polypeptide, thereby making the active site inaccessible to substrate such that normal biological activity is prevented. Examples of small molecules include but are not limited to small peptides or peptide-like molecules.
  • ITGBL1 plasmid was transfected into Cos7 cells using FuGene 6 transfection reagent (Roche diagnostics). Two days later, cells were lysed and protein extracts were subjected to SDS-PAGE migration. V5-tagged
  • RNAs were extracted at days 0, 2, 7, 14, and 21.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Analytical Chemistry (AREA)
  • Zoology (AREA)
  • Genetics & Genomics (AREA)
  • Wood Science & Technology (AREA)
  • Physics & Mathematics (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Molecular Biology (AREA)
  • Hospice & Palliative Care (AREA)
  • Biophysics (AREA)
  • Oncology (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La présente invention porte sur un procédé, et sur des produits de diagnostic des maladies osseuses utilisant des marqueurs de gènes spécifiques de la métastase osseuse tels que ITGBL-1.
PCT/EP2005/056636 2004-12-10 2005-12-09 Itgbl-1 utile comme cible regulant la metastase osseuse et le developpement osseux Ceased WO2006061430A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US63459704P 2004-12-10 2004-12-10
US60/634,597 2004-12-10

Publications (2)

Publication Number Publication Date
WO2006061430A2 true WO2006061430A2 (fr) 2006-06-15
WO2006061430A3 WO2006061430A3 (fr) 2006-08-03

Family

ID=36088317

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2005/056636 Ceased WO2006061430A2 (fr) 2004-12-10 2005-12-09 Itgbl-1 utile comme cible regulant la metastase osseuse et le developpement osseux

Country Status (1)

Country Link
WO (1) WO2006061430A2 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1754795A1 (fr) * 2005-08-02 2007-02-21 Veridex, LLC Prédiction des métastases osseuses après cancer du sein
EP2370091B1 (fr) * 2008-12-05 2017-04-12 Whitehead Institute for Biomedical Research Compositions et procédés concernant le mir-31

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040009481A1 (en) * 2001-06-11 2004-01-15 Millennium Pharmaceuticals, Inc. Compositions, kits, and methods for identification, assessment, prevention, and therapy of human prostate cancer
US7171311B2 (en) * 2001-06-18 2007-01-30 Rosetta Inpharmatics Llc Methods of assigning treatment to breast cancer patients
JP4874549B2 (ja) * 2002-12-05 2012-02-15 ザ ボード オブ トラスティーズ オブ ザ ユニヴァーシティー オブ アーカンソー システム 骨髄腫骨疾患の分子決定因子およびその用途
WO2004063355A2 (fr) * 2003-01-10 2004-07-29 Protein Design Labs, Inc. Nouveaux procedes de diagnostic d'un cancer metastatique, compositions et procedes de depister des modulateurs du cancer metastatique
EP1620567A1 (fr) * 2003-04-15 2006-02-01 Hans-Jürgen Thiesen Methode de diagnostic de la polyarthrite rhumatoide ou de l' osteoarthrite

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1754795A1 (fr) * 2005-08-02 2007-02-21 Veridex, LLC Prédiction des métastases osseuses après cancer du sein
EP2370091B1 (fr) * 2008-12-05 2017-04-12 Whitehead Institute for Biomedical Research Compositions et procédés concernant le mir-31

Also Published As

Publication number Publication date
WO2006061430A3 (fr) 2006-08-03

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