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Johansson, Anna, 2011. 4-1BB is up-regulated in human mast cells, when exposed to tumor conditioned medium . Second cycle, A1N, A1F or AXX ( AXX). Uppsala: SLU, Dept. of Anatomy, Physiology and Biochemistry

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Abstract

Mast cells have for a long time been known to accumulate around tumors (Maltby et al., 2009). Studies show that they may be important and sometimes essential in tumor angiogenesis, tumor growth and metastasis of tumors (Soucek, et al., 2007; Xiang et al., 2010). In an expression array study (Wensman et al, submitted manuscript) performed on mouse mast cells exposed to tumor conditioned medium, the gene 4-1BB was among the most up-regulated genes compared to control medium. 4-1BB codes for a membrane receptor protein of the tumor necrosis factor superfamily and has been shown to be important in T cell regulation in tumor diseases. This study was performed to investigate if human mast cells up-regulate 4-1BB when they get exposed to tumor conditioned medium. Two human mast cell lines were used: HMC-1 and Lad-2. When comparing them, Lad-2 had a more clear response to tumor conditioned medium and showed higher expression of 4-1BB. Two different tumor cell lines were used for studying the mast cell response to tumors: The thyroid carcinoma cell line Kat-4 and the melanoma cell line SK-MEL-30. Using Kat-4 to stimulate the human mast cells led to an up-regulated gene expression of 4-1BB while the use of SK-MEL-30 as a stimulant did not. The gene expression of 4-1BB in Lad-2 peaked after four hours of stimulation with serum free medium conditioned with Kat-4 cells. After twenty-four hours the gene expression of 4-1BB decreased, which is a pattern that followed what Nishimoto Et al. showed in 2005 where expression of 4-1BB was investigated in mouse mast cells. Protein expression of 4-1BB was measured after zero, four and twenty-four hours. No up-regulated protein expression of 4-1BB was observed in neither HMC-1 cells nor Lad-2 cells after stimulation with tumor cell line conditioned medium, however there was an increase of 4-1BB protein in response to calcium ionophore. In this study human mast cells responded to stimulation of tumor factors by significantly up-regulate the gene 4-1BB. Further, a correlation between expression of 4-1BB mRNA and 4-1BB protein was not observed.

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Det har länge varit känt att mastceller ansamlas runt tumörer (Maltby et al., 2009). Studier visar att de kan vara viktiga och ibland nödvändiga för kärlnybildning, tumörtillväxt och tumörspridning (Soucek, et al., 2007; Xiang et al., 2010). Vid ett experiment (Wensman et al, insänt manuskript) med mastceller från mus som inkuberades i tumörstimulerat medium visade sig 4-1BB vara en av de gener som uppreglerades mest jämfört med kontrollmedium. 4-1BB är ett membranprotein i tumörnekrosfaktorsuperfamiljen som kodar för en receptor viktig i t-cellsreglering vid tumörsjukdom. Den här studien syftar till att undersöka huruvida humana mastceller uppreglerar 4-1BB när de exponeras för tumörkonditionerat medium. Två humana mastcellinjer användes: HMC-1 och Lad-2. När de jämfördes visade Lad-2 en tydligare respons på tumörkonditionerat medium och ett högre uttryck av 4-1BB. Två olika tumörcellinjer användes: Thyroideacarcinomcellinjen Kat-4 och melanomcellinjen SK-MEL-30. Genuttrycket av 4-1BB var som högst hos Lad-2-celler efter fyra timmars stimulering i serumfritt medium konditionerat med Kat-4-celler. Efter tjugofyra timmar sjönk genuttrycket av 4-1BB vilket följer mönstret som bl.a. ses i en studie av Nishimoto Et al. från 2005 där uttrycket av 4-1BB hos musmastceller studerades. Proteinuttryck av 4-1BB mättes efter noll, fyra och tjugofyra timmar. Inget uppreglerat proteinutryck av 4-1BB observerades i vare sig HMC-1-celler eller Lad-2-celler efter stimulering med tumörcellinjekonditionerat medium, däremot noterades en ökning av 4-1BB protein som respons på kalciumjonofor. I denna studie svarade humana mastceller på stimulering med faktorer utsöndrade från tumörceller genom att signifikant uppreglera genen 4-1BB. Däremot observerades ingen korrelation mellan uttryck av 4-1BB mRNA och 4-1BB protein.

Main title:4-1BB is up-regulated in human mast cells, when exposed to tumor conditioned medium
Authors:Johansson, Anna
Supervisor:Wensman, Helena and Pejler, Gunnar
Examiner:Eriksson, Staffan
Series:Examensarbete (Sveriges lantbruksuniversitet, Fakulteten för veterinärmedicin och husdjursvetenskap, Veterinärprogrammet)
Volume/Sequential designation:2011:47
Year of Publication:2011
Level and depth descriptor:Second cycle, A1N, A1F or AXX
Student's programme affiliation:3050A Veterinary Medicine Programme (admitted before July 1, 2007) 330 HEC
Department:(VH) > Dept. of Anatomy, Physiology and Biochemistry
Keywords:tumor, cancer, mast cell, 4-1BB, gene expression, protein expression
URN:NBN:urn:nbn:se:slu:epsilon-s-697
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-s-697
Subjects:Animal physiology and biochemistry
Human medicine, health, and safety
Language:English
Deposited On:27 Oct 2011 10:26
Metadata Last Modified:20 Apr 2012 14:23

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