Fueling the flames of colon cancer – does CRP play a direct pro-inflammatory role?
BackgroundSystemic inflammation, diagnostically ascribed by measuring serum levels of the acute phase reactant C-reactive protein (CRP), has consistently been correlated with poor outcomes across cancer types. CRP exists in two structurally and functionally distinct isoforms, circulating pentameric...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1170443/full |
| _version_ | 1827987774169415680 |
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| author | Anne Helene Køstner Anne Helene Køstner Anniken Jørlo Fuglestad Anniken Jørlo Fuglestad Jeanette Baehr Georgsen Patricia Switten Nielsen Patricia Switten Nielsen Kristina Bang Christensen Helle Zibrandtsen Erik Thorlund Parner Ibraheem M. Rajab Lawrence A. Potempa Torben Steiniche Christian Kersten Christian Kersten |
| author_facet | Anne Helene Køstner Anne Helene Køstner Anniken Jørlo Fuglestad Anniken Jørlo Fuglestad Jeanette Baehr Georgsen Patricia Switten Nielsen Patricia Switten Nielsen Kristina Bang Christensen Helle Zibrandtsen Erik Thorlund Parner Ibraheem M. Rajab Lawrence A. Potempa Torben Steiniche Christian Kersten Christian Kersten |
| author_sort | Anne Helene Køstner |
| collection | DOAJ |
| description | BackgroundSystemic inflammation, diagnostically ascribed by measuring serum levels of the acute phase reactant C-reactive protein (CRP), has consistently been correlated with poor outcomes across cancer types. CRP exists in two structurally and functionally distinct isoforms, circulating pentameric CRP (pCRP) and the highly pro-inflammatory monomeric isoform (mCRP). The aim of this pilot study was to map the pattern of mCRP distribution in a previously immunologically well-defined colon cancer (CC) cohort and explore possible functional roles of mCRP within the tumor microenvironment (TME).MethodsFormalin-fixed, paraffin-embedded (FFPE) tissue samples from 43 stage II and III CC patients, including 20 patients with serum CRP 0-1 mg/L and 23 patients with serum CRP >30 mg/L were immunohistochemically (IHC) stained with a conformation-specific mCRP antibody and selected immune and stromal markers. A digital analysis algorithm was developed for evaluating mCRP distribution within the primary tumors and adjacent normal colon mucosa.ResultsmCRP was abundantly present within tumors from patients with high serum CRP (>30 mg/L) diagnostically interpreted as being systemically inflamed, whereas patients with CRP 0-1 mg/L exhibited only modest mCRP positivity (median mCRP per area 5.07‰ (95%CI:1.32-6.85) vs. 0.02‰ (95%CI:0.01-0.04), p<0.001). Similarly, tissue-expressed mCRP correlated strongly with circulating pCRP (Spearman correlation 0.81, p<0.001). Importantly, mCRP was detected exclusively within tumors, whereas adjacent normal colon mucosa showed no mCRP expression. Double IHC staining revealed colocalization of mCRP with endothelial cells and neutrophils. Intriguingly, some tumor cells also colocalized with mCRP, suggesting a direct interaction or mCRP expression by the tumor itself.ConclusionOur data show that the pro-inflammatory mCRP isoform is expressed in the TME of CC, primarily in patients with high systemic pCRP values. This strengthens the hypothesis that CRP might not only be an inflammatory marker but also an active mediator within tumors. |
| first_indexed | 2024-04-09T23:52:17Z |
| format | Article |
| id | doaj.art-3bfb2f7cc97844a19c9dcda2c9d9d27b |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-09T23:52:17Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-3bfb2f7cc97844a19c9dcda2c9d9d27b2023-03-17T05:10:57ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-03-011410.3389/fimmu.2023.11704431170443Fueling the flames of colon cancer – does CRP play a direct pro-inflammatory role?Anne Helene Køstner0Anne Helene Køstner1Anniken Jørlo Fuglestad2Anniken Jørlo Fuglestad3Jeanette Baehr Georgsen4Patricia Switten Nielsen5Patricia Switten Nielsen6Kristina Bang Christensen7Helle Zibrandtsen8Erik Thorlund Parner9Ibraheem M. Rajab10Lawrence A. Potempa11Torben Steiniche12Christian Kersten13Christian Kersten14Center for Cancer Treatment, Sorlandet Hospital, Kristiansand, NorwayDepartment of Clinical Science, University of Bergen, Bergen, NorwayCenter for Cancer Treatment, Sorlandet Hospital, Kristiansand, NorwayDepartment of Oncology, Akershus University Hospital, Nordbyhagen, NorwayDepartment of Pathology, Aarhus University Hospital, Aarhus, DenmarkDepartment of Pathology, Aarhus University Hospital, Aarhus, DenmarkDepartment of Clinical Medicine, Aarhus University, Aarhus, DenmarkDepartment of Pathology, Aarhus University Hospital, Aarhus, DenmarkDepartment of Clinical Medicine, Aarhus University, Aarhus, DenmarkSection for Biostatistics, Department of Public Health, Aarhus University, Aarhus, DenmarkCollege of Science, Health and Pharmacy, Roosevelt University Schaumburg, Schaumburg, IL, United StatesCollege of Science, Health and Pharmacy, Roosevelt University Schaumburg, Schaumburg, IL, United StatesDepartment of Pathology, Aarhus University Hospital, Aarhus, DenmarkCenter for Cancer Treatment, Sorlandet Hospital, Kristiansand, NorwayDepartment of Oncology, Akershus University Hospital, Nordbyhagen, NorwayBackgroundSystemic inflammation, diagnostically ascribed by measuring serum levels of the acute phase reactant C-reactive protein (CRP), has consistently been correlated with poor outcomes across cancer types. CRP exists in two structurally and functionally distinct isoforms, circulating pentameric CRP (pCRP) and the highly pro-inflammatory monomeric isoform (mCRP). The aim of this pilot study was to map the pattern of mCRP distribution in a previously immunologically well-defined colon cancer (CC) cohort and explore possible functional roles of mCRP within the tumor microenvironment (TME).MethodsFormalin-fixed, paraffin-embedded (FFPE) tissue samples from 43 stage II and III CC patients, including 20 patients with serum CRP 0-1 mg/L and 23 patients with serum CRP >30 mg/L were immunohistochemically (IHC) stained with a conformation-specific mCRP antibody and selected immune and stromal markers. A digital analysis algorithm was developed for evaluating mCRP distribution within the primary tumors and adjacent normal colon mucosa.ResultsmCRP was abundantly present within tumors from patients with high serum CRP (>30 mg/L) diagnostically interpreted as being systemically inflamed, whereas patients with CRP 0-1 mg/L exhibited only modest mCRP positivity (median mCRP per area 5.07‰ (95%CI:1.32-6.85) vs. 0.02‰ (95%CI:0.01-0.04), p<0.001). Similarly, tissue-expressed mCRP correlated strongly with circulating pCRP (Spearman correlation 0.81, p<0.001). Importantly, mCRP was detected exclusively within tumors, whereas adjacent normal colon mucosa showed no mCRP expression. Double IHC staining revealed colocalization of mCRP with endothelial cells and neutrophils. Intriguingly, some tumor cells also colocalized with mCRP, suggesting a direct interaction or mCRP expression by the tumor itself.ConclusionOur data show that the pro-inflammatory mCRP isoform is expressed in the TME of CC, primarily in patients with high systemic pCRP values. This strengthens the hypothesis that CRP might not only be an inflammatory marker but also an active mediator within tumors.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1170443/fullsystemic inflammationC-reactive protein (CRP)CRP isoformsmonomeric CRPcolon cancerimmunohistochemistry (IHC) |
| spellingShingle | Anne Helene Køstner Anne Helene Køstner Anniken Jørlo Fuglestad Anniken Jørlo Fuglestad Jeanette Baehr Georgsen Patricia Switten Nielsen Patricia Switten Nielsen Kristina Bang Christensen Helle Zibrandtsen Erik Thorlund Parner Ibraheem M. Rajab Lawrence A. Potempa Torben Steiniche Christian Kersten Christian Kersten Fueling the flames of colon cancer – does CRP play a direct pro-inflammatory role? Frontiers in Immunology systemic inflammation C-reactive protein (CRP) CRP isoforms monomeric CRP colon cancer immunohistochemistry (IHC) |
| title | Fueling the flames of colon cancer – does CRP play a direct pro-inflammatory role? |
| title_full | Fueling the flames of colon cancer – does CRP play a direct pro-inflammatory role? |
| title_fullStr | Fueling the flames of colon cancer – does CRP play a direct pro-inflammatory role? |
| title_full_unstemmed | Fueling the flames of colon cancer – does CRP play a direct pro-inflammatory role? |
| title_short | Fueling the flames of colon cancer – does CRP play a direct pro-inflammatory role? |
| title_sort | fueling the flames of colon cancer does crp play a direct pro inflammatory role |
| topic | systemic inflammation C-reactive protein (CRP) CRP isoforms monomeric CRP colon cancer immunohistochemistry (IHC) |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1170443/full |
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