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- W2890197367 abstract "Abstract Background Resistance to chemoradiation therapy (CRT) in oesophageal adenocarcinoma (OAC) is an important clinical challenge. Elucidating underlying mechanisms of treatment resistance is crucial to improving survival rates. Methods OAC tumour biopsies were collected prior to neoadjuvant CRT. Tumour conditioned media was generated by culturing human explants for 24 h. Response to treatment was determined pathologically using the Mandard Grading System. C3, CFB and MCP-1 mRNA expression was assessed by qPCR. Secreted C3, C3a and MCP-1 were measured by ELISA. An isogenic model of radioresistant OAC was established by chronically irradiating OE33 cells with clinically-relevant doses of 2 Gy X-ray radiation. C5aR and C3aR expression was determined by flow cytometry. Results We demonstrate, for the first time, that the central factor of the complement cascade, complement component 3 (C3), is expressed in OAC tumours and is increased in pre-treatment OAC biopsies from patients (n = 13) who have a subsequent poor response to neoadjuvant CRT (P < 0.05). In addition, C3 is secreted from ex vivo human OAC tumour explants (n = 13) and correlates with levels of the monocyte chemoattractant MCP-1 (P < 0.008) and complement factor B (CFB) a component of the alternative pathway of complement activation (P < 0.0001). In vitro, radioresistant OE33 R cells had increased mRNA levels of C3 (P < 0.01), CFB (P < 0.05) and MCP-1 (P < 0.05) compared to radiosensitive OE33 P cells. OEE3 R cells expressed increased levels of secreted C3 and the anaphylatoxin C3a, compared to radiosensitive OE33P cells (both P < 0.001). Furthermore, we demonstrate for the first time that the anaphylatoxin receptor C5aR is expressed by OAC cells, suggesting that OAC cells can respond to complement anaphylatoxins. Conclusion This study highlights, for the first time, a novel role for the complement cascade in the resistance of OAC to CRT and highlights C3 as a novel predictive marker of response to CRT in OAC. Disclosure All authors have declared no conflicts of interest." @default.
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- W2890197367 date "2018-09-01" @default.
- W2890197367 modified "2023-10-16" @default.
- W2890197367 title "RA10.02: A NOVEL ROLE FOR THE COMPLEMENT CASCADE IN CHEMORADIATION THERAPY RESISTANT OESOPHAGEAL ADENOCARCINOMA" @default.
- W2890197367 doi "https://doi.org/10.1093/dote/doy089.ra10.02" @default.
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