Cancer-related extracellular matrix signatures and related methods and products
Proteomic methods for identifying cancer related proteins and related products and kits are provided. The cancer specific proteins are extracellular matrix proteins that are associated with various aspects of cancer. Panels or signature sets of proteins useful in the detection, diagnosis and treatment of cancers as well as monitoring therapeutic progress in a cancer patient are provided herein along with methods for their detection and for their use in targeting imaging and/or therapeutic agents to the tumors via binding to the specified proteins. The proteins were identified using proteomics analyzes of tissue samples taken from cancer patients. In certain aspects the proteins are particularly useful in colon cancer patients.
1. A method of delivering an active agent to a tumor for treating or developing treatments, comprising
administering to a colon cancer subject having a tumor binding reagents each of which interact specifically with an extracellular matrix (ECM) protein of a set of proteins characteristic of an ECM protein signature, wherein the binding reagents are conjugated to active agents in an effective amount to deliver the active agents to the tumor, wherein the signature ECM proteins includes at least 3 of the proteins selected from an ECM protein signature defined as being characteristic of metastatic primary colon carcinoma (group 4) but not including MMP9, MMP2, SPARC and/or TGFβ1, colon carcinoma metastases (group 5) but not including SPP1, metastatic colon carcinoma (primary & secondary) (group 6) but not including CTSB and/or S100A8, or a signature whose expression is associated with colon cancer or metastatic colon cancer (group 7) but not including MMP9, MMP2, SPARC, TGFβ1, SPPI, LOXL2, CTSB and/or S100A8.
2. The method of claim 1 , wherein the binding reagent is an antibody or an antibody fragment.
3. The method of claim 1 , wherein the tumor is metastatic.
4. A method of delivering an active agent to a tumor, comprising administering to a colon cancer subject having a tumor a binding reagent which interacts specifically with an extracellular matrix (ECM) protein, wherein the binding reagent is conjugated to an active agent in an effective amount to deliver the active agent to the tumor, wherein the ECM protein is a set of proteins characteristic of metastatic primary colon carcinoma (group 4): ADAMDEC1, ADAMTSL1, ANXA13, ANXA7, C15orf44, CLEC11A, COL8A1, CSPG4, EMID1, FCN1, FGL2, FMOD, GREM1, INHBE, LEFTY1, LEFTY2, LEPRE1, LOXL1, LTBP3, LTBP4, MATN2, MEGF8, MFAP4, MFGE8, MMP11, MMP12, MMRN1, MMRN2, MUC5B, PAPLN, PLOD2, PLOD3, PLXDC2, PLXNB2, PLXND1, S100A11, S100A14, S100A16, SERPINA3, SERPINF1, SVEP1, and THSD4.
5. A method of delivering an active agent to a tumor, comprising administering to a colon cancer subject having a tumor a binding reagent which interacts specifically with an extracellular matrix (ECM) protein, wherein the binding reagent is conjugated to an active agent in an effective amount to deliver the active agent to the tumor, wherein the ECM protein is a set of proteins selected from an ECM protein signature characteristic of colon carcinoma metastases (group 5): COMP, HPX, IGFALS, BMP1, C1QTNF5, FNDC1, ANXA3, C1QC, CCL21, COL10A1, COL15A1, COL27A1, CRLF3, CTSA, CTSH, CXCL12, F12, FCN3, HABP2, IL16, ITIH2, KNG1, LAMA3, LEFTY1, MMP12, MMP7, MST1, NID1, PCOLCE, PRG4, S100A12, S100A4, S100P, SERPINA1, SERPINA3, SERPINB5, SERPINB6, SERPINB9, SERPINC1, SERPIND1, and SERPING1.
6. A method of delivering an active agent to a tumor, comprising administering to a colon cancer subject having a tumor a binding reagent which interacts specifically with an extracellular matrix (ECM) protein, wherein the binding reagent is conjugated to an active agent in an effective amount to deliver the active agent to the tumor, wherein the ECM protein is a set of proteins selected from an ECM protein signature characteristic of metastatic colon carcinoma (primary and secondary (group 6): ANXA5, HCFC1, HTRA1, LTBP2, MXRA5, ST14, COL22A1, GPC4, PXDN, SFTPD, THBS2, C1QA, C1QB, F2, PLOD1, SERPINB1, AGRN, EFEMP2, HMCN1, SERPINE2, A2M, AEBP1, ANXA1, ANXA11, ANXA4, ANXA6, COL18A1, CTSD, ECM1, ELANE, F9, FCN1, HRG, IGFBP7, ITIH1, ITIH4, LAMB3, LAMC2, LGALS9, LMAN1, PLG, S100A11, S100A6, S100A9, SERPINF1, and SERPINH1.
7. A method of delivering an active agent to a tumor, comprising administering to a colon cancer subject having a tumor a binding reagent which interacts specifically with an extracellular matrix (ECM) protein, wherein the binding reagent is conjugated to an active agent in an effective amount to deliver the active agent to the tumor, wherein the ECM protein is a set of proteins selected from an ECM protein signature whose expression is associated colon cancer or metastatic colon cancer (group 7): CLEC11A, FGL2, LOXL1, MFGE8, MRN1, MUC13, PAPLN, PLOD3, PLXNB2, S100A16, ADAMTSL1, C15orf44, CSPG4, EMID1, FCN1, FMOD, LEFTY1, LEPRE1, MEGF8, MMP11, MMP12, MMRN2, PLOD2, PLXDC2, PLXND1, S100A11, S100A14, SERPINA3, SERPINF1, SVEP1, ADAMDEC1, ANXA13, ANXA7, COL8A1, GREM1, INHBE, LEFTY2, LTBP3, LTBP4, MATN2, MFAP4, MUC5B, THSD4, COMP, HPX, IGFALS, BMP1, C1QTNF5, FNDC1, ANXA3, C1QC, CCL21, COL10A1, COL15A1, COL27A1, CRLF3, CTSA, CTSH, CXCL12, F12, FCN3, HABP2, IL16, ITIH2, KNG1, LAMA3, LEFTY1, MMP12, MMP7, MST1, NID1, PCOLCE, PRG4, S100A12, S100A4, S100P, SERPINA1, SERPINA3, SERPINB5, SERPINB6, SERPINB9, SERPINC1, SERPIND1, SERPING1, ANXA5, HCFC1, HTRA1, LTBP2, MXRA5, ST14, COL22A1, GPC4, PXDN, SFTPD, THBS2, C1QA, C1QB, F2, PLOD1, SERPINB1, AGRN, EFEMP2, HMCN1, SERPINE2, A2M, AEBP1, ANXA1, ANXA11, ANXA4, ANXA6, COL18A1, CSTB, CTSD, ECM1, ELANE, F9, FCN1, HRG, IGFBP7, ITIH1, ITIH4, LAMB3, LAMC2, LGALS9, LMAN1, PLG, S100A11, S100A6, S100A9, SERPINF1, and SERPINH1.
8. The method of claim 1 , wherein the active agent is a detectable label or a chemotherapeutic agent.