Identification of colorectal cancer metastasis markers by an angiogenesis-related cytokine-antibody array
AIM: To investigate the angiogenesis-related protein expression profile characterizing metastatic colorectal cancer (mCRC) with the aim of identifying prognostic markers. METHODS: The expression of 44 angiogenesis-secreted factors was measured by a novel cytokine antibody array methodology. The s...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | info:eu-repo/semantics/article |
| Language: | eng |
| Published: |
MDPI AG
2014
|
| Subjects: | |
| Online Access: | https://hdl.handle.net/10171/36165 |
| _version_ | 1793400391541456896 |
|---|---|
| author | Abajo, A. (Ana) Bitarte, N. (Nerea) Zarate, R. (Ruth) Boni, V. (Valentina) Lopez, I. (Inés) Gonzalez-Huarriz, M. (Marisol) Rodriguez, J. (Javier) Bandres, E. (Eva) Garcia-Foncillas, J. (Jesús) |
| author_facet | Abajo, A. (Ana) Bitarte, N. (Nerea) Zarate, R. (Ruth) Boni, V. (Valentina) Lopez, I. (Inés) Gonzalez-Huarriz, M. (Marisol) Rodriguez, J. (Javier) Bandres, E. (Eva) Garcia-Foncillas, J. (Jesús) |
| author_sort | Abajo, A. (Ana) |
| collection | DSpace |
| description | AIM:
To investigate the angiogenesis-related protein expression profile characterizing metastatic colorectal cancer (mCRC) with the aim of identifying prognostic markers.
METHODS:
The expression of 44 angiogenesis-secreted factors was measured by a novel cytokine antibody array methodology. The study evaluated vascular endothelial growth factor (VEGF) and its soluble vascular endothelial growth factor receptor (sVEGFR)-1 protein levels by enzyme immunoassay (EIA) in a panel of 16 CRC cell lines. mRNA VEGF and VEGF-A isoforms were quantified by quantitative reverse-transcription polymerase chain reaction (Q-RT-PCR) and vascular endothelial growth factor receptor (VEGFR)-2 expression was analyzed by flow cytometry.
RESULTS:
Metastasis-derived CRC cell lines expressed a distinctive molecular profile as compared with those isolated from a primary tumor site. Metastatic CRC cell lines were characterized by higher expression of angiogenin-2 (Ang-2), macrophage chemoattractant proteins-3/4 (MCP-3/4), matrix metalloproteinase-1 (MMP-1), and the chemokines interferon γ inducible T cell α chemoattractant protein (I-TAC), monocyte chemoattractant protein I-309, and interleukins interleukin (IL)-2 and IL-1α, as compared to primary tumor cell lines. In contrast, primary CRC cell lines expressed higher levels of interferon γ (IFN-γ), insulin-like growth factor-1 (IGF-1), IL-6, leptin, epidermal growth factor (EGF), placental growth factor (PlGF), thrombopoietin, transforming growth factor β1 (TGF-β1) and VEGF-D, as compared with the metastatic cell lines. VEGF expression does not significantly differ according to the CRC cellular origin in normoxia. Severe hypoxia induced VEGF expression up-regulation but contrary to expectations, metastatic CRC cell lines did not respond as much as primary cell lines to the hypoxic stimulus. In CRC primary-derived cell lines, we observed a two-fold increase in VEGF expression between normoxia and hypoxia as compared to metastatic cell lines. CRC cell lines express a similar pattern of VEGF isoforms (VEGF₁₂₁, VEGF₁₆₅ and VEGF₁₈₉) despite variability in VEGF expression, where the major transcript was VEGF₁₂₁. No relevant expression of VEGFR-2 was found in CRC cell lines, as compared to that of human umbilical vein endothelial cells and sVEGFR-1 expression did not depend on the CRC cellular origin.
CONCLUSION:
A distinct angiogenesis-related expression pattern characterizes metastatic CRC cell lines. Factors other than VEGF appear as prognostic markers and intervention targets in the metastatic CRC setting. |
| format | info:eu-repo/semantics/article |
| id | oai:dadun.unav.edu:10171-36165 |
| institution | Universidad de Navarra |
| language | eng |
| publishDate | 2014 |
| publisher | MDPI AG |
| record_format | dspace |
| spelling | oai:dadun.unav.edu:10171-361652020-03-04T00:42:28Z Identification of colorectal cancer metastasis markers by an angiogenesis-related cytokine-antibody array Abajo, A. (Ana) Bitarte, N. (Nerea) Zarate, R. (Ruth) Boni, V. (Valentina) Lopez, I. (Inés) Gonzalez-Huarriz, M. (Marisol) Rodriguez, J. (Javier) Bandres, E. (Eva) Garcia-Foncillas, J. (Jesús) Colorectal cancer metastasis Cytokine-antibody array Angiogenesis Vascular endothelial growth factor Biomarkers AIM: To investigate the angiogenesis-related protein expression profile characterizing metastatic colorectal cancer (mCRC) with the aim of identifying prognostic markers. METHODS: The expression of 44 angiogenesis-secreted factors was measured by a novel cytokine antibody array methodology. The study evaluated vascular endothelial growth factor (VEGF) and its soluble vascular endothelial growth factor receptor (sVEGFR)-1 protein levels by enzyme immunoassay (EIA) in a panel of 16 CRC cell lines. mRNA VEGF and VEGF-A isoforms were quantified by quantitative reverse-transcription polymerase chain reaction (Q-RT-PCR) and vascular endothelial growth factor receptor (VEGFR)-2 expression was analyzed by flow cytometry. RESULTS: Metastasis-derived CRC cell lines expressed a distinctive molecular profile as compared with those isolated from a primary tumor site. Metastatic CRC cell lines were characterized by higher expression of angiogenin-2 (Ang-2), macrophage chemoattractant proteins-3/4 (MCP-3/4), matrix metalloproteinase-1 (MMP-1), and the chemokines interferon γ inducible T cell α chemoattractant protein (I-TAC), monocyte chemoattractant protein I-309, and interleukins interleukin (IL)-2 and IL-1α, as compared to primary tumor cell lines. In contrast, primary CRC cell lines expressed higher levels of interferon γ (IFN-γ), insulin-like growth factor-1 (IGF-1), IL-6, leptin, epidermal growth factor (EGF), placental growth factor (PlGF), thrombopoietin, transforming growth factor β1 (TGF-β1) and VEGF-D, as compared with the metastatic cell lines. VEGF expression does not significantly differ according to the CRC cellular origin in normoxia. Severe hypoxia induced VEGF expression up-regulation but contrary to expectations, metastatic CRC cell lines did not respond as much as primary cell lines to the hypoxic stimulus. In CRC primary-derived cell lines, we observed a two-fold increase in VEGF expression between normoxia and hypoxia as compared to metastatic cell lines. CRC cell lines express a similar pattern of VEGF isoforms (VEGF₁₂₁, VEGF₁₆₅ and VEGF₁₈₉) despite variability in VEGF expression, where the major transcript was VEGF₁₂₁. No relevant expression of VEGFR-2 was found in CRC cell lines, as compared to that of human umbilical vein endothelial cells and sVEGFR-1 expression did not depend on the CRC cellular origin. CONCLUSION: A distinct angiogenesis-related expression pattern characterizes metastatic CRC cell lines. Factors other than VEGF appear as prognostic markers and intervention targets in the metastatic CRC setting. 2014-07-15T11:29:26Z 2014-07-15T11:29:26Z 2012 info:eu-repo/semantics/article https://hdl.handle.net/10171/36165 eng info:eu-repo/semantics/openAccess application/pdf MDPI AG |
| spellingShingle | Colorectal cancer metastasis Cytokine-antibody array Angiogenesis Vascular endothelial growth factor Biomarkers Abajo, A. (Ana) Bitarte, N. (Nerea) Zarate, R. (Ruth) Boni, V. (Valentina) Lopez, I. (Inés) Gonzalez-Huarriz, M. (Marisol) Rodriguez, J. (Javier) Bandres, E. (Eva) Garcia-Foncillas, J. (Jesús) Identification of colorectal cancer metastasis markers by an angiogenesis-related cytokine-antibody array |
| title | Identification of colorectal cancer metastasis markers by an angiogenesis-related cytokine-antibody array |
| title_full | Identification of colorectal cancer metastasis markers by an angiogenesis-related cytokine-antibody array |
| title_fullStr | Identification of colorectal cancer metastasis markers by an angiogenesis-related cytokine-antibody array |
| title_full_unstemmed | Identification of colorectal cancer metastasis markers by an angiogenesis-related cytokine-antibody array |
| title_short | Identification of colorectal cancer metastasis markers by an angiogenesis-related cytokine-antibody array |
| title_sort | identification of colorectal cancer metastasis markers by an angiogenesis-related cytokine-antibody array |
| topic | Colorectal cancer metastasis Cytokine-antibody array Angiogenesis Vascular endothelial growth factor Biomarkers |
| url | https://hdl.handle.net/10171/36165 |
| work_keys_str_mv | AT abajoaana identificationofcolorectalcancermetastasismarkersbyanangiogenesisrelatedcytokineantibodyarray AT bitartennerea identificationofcolorectalcancermetastasismarkersbyanangiogenesisrelatedcytokineantibodyarray AT zaraterruth identificationofcolorectalcancermetastasismarkersbyanangiogenesisrelatedcytokineantibodyarray AT bonivvalentina identificationofcolorectalcancermetastasismarkersbyanangiogenesisrelatedcytokineantibodyarray AT lopeziines identificationofcolorectalcancermetastasismarkersbyanangiogenesisrelatedcytokineantibodyarray AT gonzalezhuarrizmmarisol identificationofcolorectalcancermetastasismarkersbyanangiogenesisrelatedcytokineantibodyarray AT rodriguezjjavier identificationofcolorectalcancermetastasismarkersbyanangiogenesisrelatedcytokineantibodyarray AT bandreseeva identificationofcolorectalcancermetastasismarkersbyanangiogenesisrelatedcytokineantibodyarray AT garciafoncillasjjesus identificationofcolorectalcancermetastasismarkersbyanangiogenesisrelatedcytokineantibodyarray |