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[{"key": "dc.contributor.advisor", "value": "Pasonen-Sepp\u00e4nen, Sanna", "language": "", "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.advisor", "value": "Ketola, Kirsi", "language": "", "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.author", "value": "Hartikainen, Kiia", "language": "", "element": "contributor", "qualifier": "author", "schema": "dc"}, {"key": "dc.date.accessioned", "value": "2023-06-05T11:43:49Z", "language": null, "element": "date", "qualifier": "accessioned", "schema": "dc"}, {"key": "dc.date.available", "value": "2023-06-05T11:43:49Z", "language": null, "element": "date", "qualifier": "available", "schema": "dc"}, {"key": "dc.date.issued", "value": "2023", "language": "", "element": "date", "qualifier": "issued", "schema": "dc"}, {"key": "dc.identifier.uri", "value": "https://jyx.jyu.fi/handle/123456789/87441", "language": null, "element": "identifier", "qualifier": "uri", "schema": "dc"}, {"key": "dc.description.abstract", "value": "Sy\u00f6p\u00e4kasvaimen mikroymp\u00e4rist\u00f6 koostuu sy\u00f6p\u00e4solujen ja sy\u00f6p\u00e4kantasolujen lis\u00e4ksi monista kasvaimen kasvua ja levi\u00e4mist\u00e4 edist\u00e4vist\u00e4 soluista sek\u00e4 solujen tuottamasta soluv\u00e4liaineesta. M1- tai M2-tyypiksi polarisoituvat makrofagit ovat yksi kasvaimen mikroymp\u00e4rist\u00f6ss\u00e4 runsaana esiintyvist\u00e4 solutyypeist\u00e4. Kasvaimen mikroymp\u00e4rist\u00f6n soluv\u00e4liaineessa esiintyy runsaasti my\u00f6s solujen eritt\u00e4m\u00e4\u00e4 hyaluronaania (HA), joka vaikuttaa kiihdytt\u00e4v\u00e4sti sy\u00f6p\u00e4kasvaimen kasvuun ja levi\u00e4miseen. Sy\u00f6p\u00e4kantasolut vaikuttavat my\u00f6s keskeisesti sy\u00f6v\u00e4n pahanlaatuisuuteen. T\u00e4ss\u00e4 Pro gradu - tutkielmassa tutkittiin, kuinka M1-makrofagit vaikuttavat sy\u00f6p\u00e4solujen kantasolumaistumiseen, ja mit\u00e4 signalointireittej\u00e4 pitkin makrofagien eritt\u00e4m\u00e4t tekij\u00e4t indusoivat sy\u00f6p\u00e4solujen muuntumista sy\u00f6p\u00e4kantasoluiksi. Tutkimuksen kohteena k\u00e4ytettiin THP-1 -soluista polarisoituja makrofageja, LNCaP C4-2B eturauhassy\u00f6p\u00e4soluja ja SCC9 kielen levyepiteelikarsinoomasoluja. Tutkimuksessa THP-1 -solut polarisoitiin M1-tyypin makrofageiksi, ja M1-makrofagien kasvatusmedium ker\u00e4ttiin steriilisuodatettuna (M1 CM). Sy\u00f6p\u00e4solut k\u00e4siteltiin M1- makrofagien kasvatusmediumilla. Makrofagik\u00e4sitellyille sy\u00f6p\u00e4soluille suoritettiin my\u00f6s eri signalointireittej\u00e4 inhiboivia inhibiittorik\u00e4sittelyj\u00e4 ja k\u00e4sittelyj\u00e4 pienell\u00e4 CD44-proteiinin ekspressiota h\u00e4iritsev\u00e4ll\u00e4 RNA:lla, CD44 siRNA:lla. Makrofagien eritt\u00e4mien tekij\u00f6iden, inhibiittorien ja CD44 siRNA:n vaikutusta sy\u00f6p\u00e4kantasolumarkkerien ja HA-syntaasien ekspressioon selvitettiin reaaliaikaisella kvantitatiivisella PCR:ll\u00e4, RT-qPCR:ll\u00e4. Tulokset osoittivat, ett\u00e4 M1 CM -k\u00e4sittely nosti sy\u00f6p\u00e4kantasolumarkkerien ja HA-syntaasien ekspressiota LNCaP C4-2B ja SCC9- soluilla. CD44 siRNA -k\u00e4sittely ei laskenut sy\u00f6p\u00e4kantasolumarkkerien ja HA- syntaasien ekspressiota SCC9-soluilla. Sek\u00e4 LNCaP C4-2B \u2013 ett\u00e4 SCC9-soluilla WNT974- ja IKK16-inhibiittorik\u00e4sittelyt sek\u00e4 SCC9-soluilla U0126-inhibiittorik\u00e4sittely laskivat sy\u00f6p\u00e4kantasolumarkkerien ja HA-syntaasien ekspressiota. Johtop\u00e4\u00e4t\u00f6ksen\u00e4 voidaan todeta, ett\u00e4 M1-makrofagit edist\u00e4v\u00e4t sy\u00f6p\u00e4kantasolujen muodostumista. Lis\u00e4\u00e4 tutkimusta kuitenkin tarvitaan erityisesti siit\u00e4, mit\u00e4 signalointireittej\u00e4 pitkin makrofagien eritt\u00e4mien tekij\u00f6iden aikaansaama sy\u00f6p\u00e4kantasolumarkkerien ja HA- syntaasien ekspressioon johtava signalointi tapahtuu.", "language": "fi", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.abstract", "value": "The tumor microenvironment consists of cancer cells and cancer stem cells, but also many other cell types which promote tumor progression and metastasis, and the extracellular matrix produced by cells. M1 and M2 macrophages are abundant cell types in the tumor microenvironment. Cells secrete hyaluronan (HA) into their extracellular matrix, and therefore also hyaluronan can be found abundantly in the tumor microenvironment. Hyaluronan has shown to stimulate the progression and metastasis of several tumor types. Cancer stem cells are also crucial actors affecting the malignant features of cancer. In this MSc thesis it was studied whether M1 macrophages affect the transformation of cancer cells into cancer stem cells, and what are the signaling pathways leading to cancer stem cell marker expression, that the secreted factors of macrophages induce. Macrophages polarized from THP-1 cells, LNCaP C4-2B prostate cancer cells and SCC9 oral squamous cell carcinoma cells were used as targets in this study. In this study, THP-1 cells were polarized into M1 macrophages, and the cell culture medium of M1 macrophages was collected and sterile filtered (M1 CM). Cancer cells were treated with the cell culture medium of M1 macrophages. Also, treatments with inhibitors of different signaling pathways, and small interfering RNA targeting CD44 protein, CD44 siRNA, were performed on the macrophage-treated cancer cells. The effects of the factors secreted by macrophages, inhibitor treatments and CD44 siRNA treatment to the expression of cancer stem cell markers and HA synthases were examined using real-time quantitative PCR, RT- qPCR. Results show that M1 macrophages increased the expression of cancer stem cell markers and HA synthases in both LNCaP C4-2B cells and SCC9 cells. CD44 siRNA treatment did not decrease the expression of cancer stem cell markers and HA synthases in SCC9 cells. WNT974 and IKK16 inhibitors in both LNCaP C4-2B cells and SCC9 cells and U0126 inhibitor in SCC9 cells decreased the expression of cancer stem cell markers and HA synthases. In conclusion, M1 macrophages drive the formation of cancer stem cells. More research is still needed, especially about the signaling pathways that lead to increased expression of cancer stem cell markers and HA synthases.", "language": "en", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Submitted by Miia Hakanen (mihakane@jyu.fi) on 2023-06-05T11:43:49Z\nNo. of bitstreams: 0", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Made available in DSpace on 2023-06-05T11:43:49Z (GMT). No. of bitstreams: 0\n Previous issue date: 2023", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.format.extent", "value": "34", "language": "", "element": "format", "qualifier": "extent", "schema": "dc"}, {"key": "dc.language.iso", "value": "fin", "language": null, "element": "language", "qualifier": "iso", "schema": "dc"}, {"key": "dc.rights", "value": "In Copyright", "language": null, "element": "rights", "qualifier": null, "schema": "dc"}, {"key": "dc.subject.other", "value": "tuumori", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "tuumorin aloittajasolut", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "tuumorin mikroymp\u00e4rist\u00f6", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.title", "value": "Pro-inflammatoristen M1-makrofagien vaikutus sy\u00f6p\u00e4kantasolujen muodostumiseen", "language": "", "element": "title", "qualifier": null, "schema": "dc"}, {"key": "dc.type", "value": "master thesis", "language": null, "element": "type", "qualifier": null, "schema": "dc"}, {"key": "dc.identifier.urn", "value": "URN:NBN:fi:jyu-202306053504", "language": "", "element": "identifier", "qualifier": "urn", "schema": "dc"}, {"key": "dc.type.ontasot", "value": "Master\u2019s thesis", "language": "en", "element": "type", "qualifier": "ontasot", "schema": "dc"}, {"key": "dc.type.ontasot", "value": "Pro gradu -tutkielma", "language": "fi", "element": "type", "qualifier": "ontasot", "schema": "dc"}, {"key": "dc.contributor.faculty", "value": "Matemaattis-luonnontieteellinen tiedekunta", "language": "fi", "element": "contributor", "qualifier": "faculty", "schema": "dc"}, {"key": "dc.contributor.faculty", "value": "Faculty of Sciences", "language": "en", "element": "contributor", "qualifier": "faculty", "schema": "dc"}, {"key": "dc.contributor.department", "value": "Bio- ja ymp\u00e4rist\u00f6tieteiden laitos", "language": "fi", "element": "contributor", "qualifier": "department", "schema": "dc"}, {"key": "dc.contributor.department", "value": "Department of Biological and Environmental Science", "language": "en", "element": "contributor", "qualifier": "department", "schema": "dc"}, {"key": "dc.contributor.organization", "value": "Jyv\u00e4skyl\u00e4n yliopisto", "language": "fi", "element": "contributor", "qualifier": "organization", "schema": "dc"}, {"key": "dc.contributor.organization", "value": "University of Jyv\u00e4skyl\u00e4", "language": "en", "element": "contributor", "qualifier": "organization", "schema": "dc"}, {"key": "dc.subject.discipline", "value": "Solu- ja molekyylibiologia", "language": "fi", "element": "subject", "qualifier": "discipline", "schema": "dc"}, {"key": "dc.subject.discipline", "value": "Cell and molecular biology", "language": "en", "element": "subject", "qualifier": "discipline", "schema": "dc"}, {"key": "yvv.contractresearch.funding", "value": "0", "language": "", "element": "contractresearch", "qualifier": "funding", "schema": "yvv"}, {"key": "dc.type.coar", "value": "http://purl.org/coar/resource_type/c_bdcc", "language": null, "element": "type", "qualifier": "coar", "schema": "dc"}, {"key": "dc.rights.copyright", "value": "\u00a9 The Author(s)", "language": null, "element": "rights", "qualifier": "copyright", "schema": "dc"}, {"key": "dc.rights.accesslevel", "value": "restrictedAccess", "language": null, "element": "rights", "qualifier": "accesslevel", "schema": "dc"}, {"key": "dc.type.publication", "value": "masterThesis", "language": null, "element": "type", "qualifier": "publication", "schema": "dc"}, {"key": "dc.subject.oppiainekoodi", "value": "4013", "language": "", "element": "subject", "qualifier": "oppiainekoodi", "schema": "dc"}, {"key": "dc.subject.yso", "value": "monosyytit", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "sy\u00f6p\u00e4taudit", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "kantasolut", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.rights.url", "value": "https://rightsstatements.org/page/InC/1.0/", "language": null, "element": "rights", "qualifier": "url", "schema": "dc"}, {"key": "dc.rights.accessrights", "value": "The author has not given permission to make the work publicly available electronically. Therefore the material can be read only at the archival workstation at Jyv\u00e4skyl\u00e4 University Library (https://kirjasto.jyu.fi/collections/archival-workstation).", "language": "en", "element": "rights", "qualifier": "accessrights", "schema": "dc"}, {"key": "dc.rights.accessrights", "value": "Tekij\u00e4 ei ole antanut lupaa avoimeen julkaisuun, joten aineisto on luettavissa vain Jyv\u00e4skyl\u00e4n yliopiston kirjaston arkistoty\u00f6semalta. Ks. https://kirjasto.jyu.fi/kokoelmat/arkistotyoasema..", "language": "fi", "element": "rights", "qualifier": "accessrights", "schema": "dc"}]
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