title: Downregulation of Prominin 1/CD133 expression in colorectal cancer by             NSAIDs following short-term preoperative treatment.
abstract: Expression of Prominin 1/CD133 is associated with poor prognosis and chemoresistance in several types of solid tumors. The aim of the present study was, therefore, to evaluate Prominin 1/CD133 expression in colorectal carcinoma after short-term preoperative treatment by non-steroidal anti-inflammatory drugs (NSAIDs). Patients aimed at curative operation for colon cancer were randomized to receive NSAIDs (indomethacin 50 mg x2 or celecoxib 100 mg x2) three days preoperatively. Antisecretory prophylaxis (esomeprasol 40 mg x1) was provided to all patients and served as sham intake. CD133 expression in tumor tissue was also assessed in tumors from Dukes' B patients selected for either long or short postoperative survival. No patients received perioperative chemoradiotherapy. Tumor tissue was collected at surgery for quantification of mRNAs (Prom1 and Wnt4) by qPCR. Immunohistochemistry stained for CD133, Ep-CAM, CD34 and CD45. PGE2 content in tumor tissue was determined. Transcript of CD133 in tumor tissue was lower in patients treated with NSAIDs (0.28 ± 0.07 vs. 0.51 ± 0.08; p<0.03) as well as some other stem cell-related transcripts. In treated patients 36% of all tumors stained positive for CD133 compared to 71% in sham-treated control patients (p<0.05). Short survivors with Dukes' B tumors displayed 78% CD133 expression as compared to 33% of tumors in long-term survivors (p<0.002). Tumor tissue PGE(2) content was negatively related to patient survival. Our results show that short-term preoperative NSAID treatment downregulates colon cancer tissue expression of Prominin 1/CD133, a stem cell marker indicative of survival prognosis as confirmed.
authors.affiliation: Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, Surgical Metabolic Research Laboratory at Lundberg Laboratory for Cancer Research, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden. christina.lonnroth@surgery.gu.se
authors.forename: Christina
authors.initials: C
authors.lastname: Lönnroth
authors.forename: Marianne
authors.initials: M
authors.lastname: Andersson
authors.forename: Svante
authors.initials: S
authors.lastname: Nordgren
authors.forename: Kent
authors.initials: K
authors.lastname: Lundholm
mesh_terms: D000071916:AC133 Antigen; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000068579:Celecoxib; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D003131:Combined Modality Therapy; D015232:Dinoprostone / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000235:genetics* / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D060888:Real-Time Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use; D014158:Transcription, Genetic
chemical_list: D000071916:AC133 Antigen; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib; D015232:Dinoprostone; D007213:Indomethacin