Evaluation of CAIX and CAXII Expression in Breast Cancer at Varied O2 Levels: CAIX is the Superior Surrogate Imaging Biomarker of Tumor Hypoxia.
Purpose: Hypoxia is commonly observed in regions of primary tumors and metastases, and is associated with resistance to treatment, more aggressive tumor phenotypes and poor prognosis. Reliable and validated imaging biomarkers of hypoxia are needed for pre-clinical studies and clinical use. Expressio...
| Publicado en: | Molecular Imaging & Biology Vol. 18; no. 2; pp. 219 - 232 |
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| Autores principales: | , , , , , , , , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Springer Nature
Apr2016
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=113577018&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 113577018 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 15361632 KJU jtl: Molecular Imaging & Biology issn: 15361632 maglogo: N pubinfo: dt: Apr2016 vid: 18 iid: 2 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 113577018 113577018 NLM26276155 113577018 10.1007/s11307-015-0885-x NLM26276155 PMC4754166 [Available on 04/01/17] 113577018 ppf: 219 ppct: 13 formats: fmt: @attributes: type: P tig: atl: Evaluation of CAIX and CAXII Expression in Breast Cancer at Varied O2 Levels: CAIX is the Superior Surrogate Imaging Biomarker of Tumor Hypoxia. aug: au: Tafreshi, Narges Lloyd, Mark Proemsey, Joshua Bui, Marilyn Kim, Jongphil Gillies, Robert Morse, David Tafreshi, Narges K Lloyd, Mark C Proemsey, Joshua B Bui, Marilyn M Gillies, Robert J Morse, David L affil: Department of Cancer Imaging & Metabolism, H. Lee Moffitt Cancer Center and Research Institute, Tampa 33612 USA sug: subj: Antigens, Tumor Metabolism Breast Neoplasms Molecular Imaging Methods Oxygen Pharmacodynamics Carbonic Anhydrases Metabolism Analysis of Variance Mice Antigens, Tumor Genes Drug Effects Female Breast Neoplasms Pathology RNA Metabolism Tomography Light Cell Line, Tumor Animal Studies RNA Carbonic Anhydrases Funding Source Female ab: Purpose: Hypoxia is commonly observed in regions of primary tumors and metastases, and is associated with resistance to treatment, more aggressive tumor phenotypes and poor prognosis. Reliable and validated imaging biomarkers of hypoxia are needed for pre-clinical studies and clinical use. Expression of cell-surface carbonic anhydrases IX and XII (CAIX and CAXII) in tumor cells has been associated with tumor hypoxia. CAIX and CAXII specific antibodies conjugated to fluorescent dye were evaluated for the non-invasive detection of hypoxia in vivo.Procedures: Human breast cancer cell lines (MCF10A, DCIS, MCF7, ZR-75.1 and MDA-mb231) were characterized for CAIX and CAXII expression by real-time RT-PCR and immunocytochemistry (ICC) under normoxic and hypoxic conditions. Immunohistochemical (IHC) staining of CAIX, CAXII and the commercially available exogenous hypoxia marker, pimonidazole, was performed using sections of ZR-75.1 and MDA-mb-231 orthotopic breast cancer xenograft tumors from nude mice. In vivo fluorescence imaging of ZR-75.1 tumors in animals housed at varied levels of oxygen was used to quantify the relative uptake of the CAIX and CAXII agents and a commercially available sulfonamide-based agent. Corresponding tumor sections were IHC stained for CAIX, CAXII and pimonidazole.Results: CAIX mRNA expression was significantly higher (p < 0.05) in hypoxia for all cell lines, which was in agreement with protein expression by ICC. CAXII expression was mixed, with a modest hypoxia-related increase in two cell lines (p < 0.05) and no change in others. Quantified IHC staining of ZR-75.1 and MDA-mb-231 tumor sections showed that CAIX and CAXII expression was elevated in regions with pimonidazole staining, but CAXII levels were lower than CAIX. Tumor uptake of the CAIX targeted agent, and IHC staining of CAIX and pimonidazole in corresponding tumor sections were correlated, and co-registered, and shown to be significantly elevated by level of oxygenation (p < 0.001): hypoxia > normoxia > hyperoxia. However, the CAXII and sulfonamide agents were not significantly correlated with hypoxia.Conclusion: These studies suggest that the fluorescently labeled CAIX-specific agent is a more robust indicator of hypoxia in vivo compared to the CAXII-specific agent or the agent specific to the CA active site. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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