title: Identification of Novel Biomarkers for Metastatic Colorectal Cancer Using Angiogenesis-Antibody Array and Intracellular Signaling Array.
abstract: Colorectal cancer (CRC) is one of the three leading causes for cancer mortality. CRC kills over 600,000 people annually worldwide. The most common cause of death from CRC is the metastasis to distant organs. However, biomarkers for CRC metastasis remain ill-defined. We compared primary and metastatic CRC cell lines for their angiogenesis-protein profiles and intracellular signaling profiles to identify novel biomarkers for CRC metastasis. To this end, we used primary and metastatic CRC cell lines as a model system and normal human colon cell line as a control. The angiogenesis profiles two isogenic CRC cell lines, SW480 and SW620, and HT-29 and T84 revealed that VEGF was upregulated in both SW620 and T84 whereas coagulation factor III, IGFBP-3, DPP IV, PDGF AA/AB, endothelin I and CXCL16 were downregulated specifically in metastatic cell lines. Furthermore, we found that TIMP-1, amphiregulin, endostatin, angiogenin were upregulated in SW620 whereas downregulated in T84. Angiogenin was downregulated in T84 and GM-CSF was also downregulated in SW620. To induce CRC cell metastasis, we treated cells with pro-inflammatory cytokine IL-6. Upon IL-6 treatment, epithelial-mesenchymal transition was induced in CRC cells. When DLD-1 and HT-29 cells were treated with IL-6; Akt, STAT3, AMPKα and Bad phosphorylation levels were increased. Interestingly, SW620 showed the same signal activation pattern with IL-6 treatment of HT-29 and DLD-1. Our data suggest that Akt, STAT3, AMPKα and Bad activation can be biomarkers for metastatic colorectal cancer. IL-6 treatment specifically reduced phosphorylation levels of EGFR, HER2 receptor, Insulin R and IGF-1R in receptor tyrosine kinase array study with HT-29. Taken together, we have identified novel biomarkers for metastatic CRC through the angiogenesis-antibody array and intracellular signaling array studies. Present study suggests that those novel biomarkers can be used as CRC prognosis biomarkers, and as potential targets for the metastatic CRC therapy.
authors.affiliation: Division of Cancer Research and Training, Department of Medicine, Charles R. Drew University of Medicine and Science, 1731 120th street, Los Angeles, California, 90059, United States of America.
authors.forename: Seyung
authors.initials: S
authors.lastname: Chung
authors.affiliation: Division of Cancer Research and Training, Department of Medicine, Charles R. Drew University of Medicine and Science, 1731 120th street, Los Angeles, California, 90059, United States of America.
authors.forename: Sami
authors.initials: S
authors.lastname: Dwabe
authors.affiliation: Division of Cancer Research and Training, Department of Medicine, Charles R. Drew University of Medicine and Science, 1731 120th street, Los Angeles, California, 90059, United States of America.
authors.forename: Yayha
authors.initials: Y
authors.lastname: Elshimali
authors.affiliation: Division of Cancer Research and Training, Department of Medicine, Charles R. Drew University of Medicine and Science, 1731 120th street, Los Angeles, California, 90059, United States of America.
authors.forename: Hemlata
authors.initials: H
authors.lastname: Sukhija
authors.affiliation: Division of Cancer Research and Training, Department of Medicine, Charles R. Drew University of Medicine and Science, 1731 120th street, Los Angeles, California, 90059, United States of America.
authors.forename: Clement
authors.initials: C
authors.lastname: Aroh
authors.affiliation: Division of Cancer Research and Training, Department of Medicine, Charles R. Drew University of Medicine and Science, 1731 120th street, Los Angeles, California, 90059, United States of America; David Geffen UCLA School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Jaydutt V
authors.initials: JV
authors.lastname: Vadgama
mesh_terms: D000906:Antibodies / Q000737:chemistry; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D019332:Endothelin-1 / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D051116:Receptors, Scavenger / Q000378:metabolism; D012259:Ribonuclease, Pancreatic / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000906:Antibodies; D014408:Biomarkers, Tumor; C423727:CXCL16 protein, human; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D019332:Endothelin-1; C515497:IGFBP3 protein, human; C508600:IL6 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D015850:Interleukin-6; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D010982:Platelet-Derived Growth Factor; D051116:Receptors, Scavenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C075278:platelet-derived growth factor A; C046366:angiogenin; D012259:Ribonuclease, Pancreatic; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4