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Open AccessArticle

Evaluation of Glycosylated PTGS2 in Colorectal Cancer for NSAIDS-Based Adjuvant Therapy

1
OU Molecular Oncology & Angiogenesis, IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132 Genoa, Italy
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OU Immunology, IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132 Genoa, Italy
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OU Cell Biology, IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132 Genoa, Italy
4
OU Oncologic Surgery and Implantable Systems, IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132 Genoa, Italy
5
OU Pathology, IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132 Genoa, Italy
6
OU Molecular Diagnostics, IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132 Genoa, Italy
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Department of Surgical Science and Integrated Diagnostics, University of Genoa, 16132 Genoa, Italy
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Clinical and Experimental Immunology lab, Ospedale G. Gaslini, 16147 Genoa, Italy
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Department of General Surgery, Asl3, Ospedale Villa Scassi, 16149 Genoa, Italy
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Department of Experimental Medicine (DIMES), University of Genoa, 16132 Genoa, Italy
*
Author to whom correspondence should be addressed.
These authors have contributed equally.
Cells 2020, 9(3), 683; https://doi.org/10.3390/cells9030683
Received: 28 November 2019 / Revised: 26 February 2020 / Accepted: 6 March 2020 / Published: 11 March 2020
(This article belongs to the Special Issue Micro- and Macro-Environmental Factors in Solid Cancers)
Observational/retrospective studies indicate that prostaglandin-endoperoxide synthase-2 (PTGS2) inhibitors could positively affect colorectal cancer (CRC) patients’ survival after diagnosis. To obtain an acceptable cost/benefit balance, the inclusion of PTGS2 inhibitors in the adjuvant setting needs a selective criterion. We quantified the 72 kDa, CRC-associated, glycosylated form of PTGS2 in 100 frozen CRC specimens and evaluated PTGS2 localization by IHC in the same tumors, scoring tumor epithelial-derived and stroma-derived fractions. We also investigated the involvement of interleukin-1 beta (IL1β) in PTGS2 induction, both in vitro and in CRC lysates. Finally, we used overall survival (OS) as a criterion for patient selection. Glycosylated PTGS2 can be quantified with high sensibility in tissue lysates, but the expression in both tumor and stromal cells limits its use for predictive purposes. Immunohistochemistry (IHC) analysis indicates that stromal PTGS2 expression could exert a protective role on patient OS. Stromal PTGS2 was prevalently expressed by cancer-associated fibroblasts exerting a barrier function near the gut lumen, and it apparently favored the antitumor M1 macrophage population. IL1β was directly linked to gPTGS2 expression both in vitro and in tumors, but its activity was apparently prevalent on the stromal cell population. We suggest that stromal PTGS2 could exert a positive effect on patients OS when expressed in the luminal area of the tumor. View Full-Text
Keywords: prostaglandin-endoperoxide synthase-2/Cyclooxygenase 2 (PTGS2/COX-2); colorectal cancer (CRC); non-steroidal anti-inflammatory drugs (NSAIDS); cancer-associated fibroblasts (CAF); interleukin-1 beta (IL1β); macrophages prostaglandin-endoperoxide synthase-2/Cyclooxygenase 2 (PTGS2/COX-2); colorectal cancer (CRC); non-steroidal anti-inflammatory drugs (NSAIDS); cancer-associated fibroblasts (CAF); interleukin-1 beta (IL1β); macrophages
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Venè, R.; Costa, D.; Augugliaro, R.; Carlone, S.; Scabini, S.; Casoni Pattacini, G.; Boggio, M.; Zupo, S.; Grillo, F.; Mastracci, L.; Pitto, F.; Minghelli, S.; Ferrari, N.; Tosetti, F.; Romairone, E.; Mingari, M.C.; Poggi, A.; Benelli, R. Evaluation of Glycosylated PTGS2 in Colorectal Cancer for NSAIDS-Based Adjuvant Therapy. Cells 2020, 9, 683.

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