Interleukin 33/ST2 Axis Components Are Associated to Desmoplasia, a Metastasis-Related Factor in Colorectal Cancer

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dc.contributor.authorLandskron, Glauben
dc.contributor.authorDe la Fuente Lopez, Marjorie
dc.contributor.authorDubois-Camacho, Karen
dc.contributor.authorDiaz-Jimenez, David
dc.contributor.authorOrellana-Serradell, Octavio
dc.contributor.authorRomero, Diego
dc.contributor.authorSepulveda, Santiago A.
dc.contributor.authorSalazar, Christian
dc.contributor.authorParada-Venegas, Daniela
dc.contributor.authorQuera, Rodrigo
dc.contributor.authorSimian, Daniela
dc.contributor.authorGonzalez, Maria-Julieta
dc.contributor.authorKronberg, Udo
dc.contributor.authorAbedrapo, Mario
dc.contributor.authorGallegos, Ivan
dc.contributor.authorContreras, Hector R.
dc.contributor.authorPena, Cristina
dc.contributor.authorDiaz-Araya, Guillermo
dc.contributor.authorCarlos Roa, Juan
dc.contributor.authorHermoso, Marcela A.
dc.date.accessioned2025-01-23T21:12:17Z
dc.date.available2025-01-23T21:12:17Z
dc.date.issued2019
dc.description.abstractIn colorectal cancer (CRC), cancer-associated fibroblasts (CAFs) are the most abundant component from the tumor microenvironment (TM). CAFs facilitate tumor progression by inducing angiogenesis, immune suppression and invasion, thus altering the organization/composition of the extracellular matrix (i.e., desmoplasia) and/or activating epithelial-mesenchymal transition (EMT). Soluble factors from the TM can also contribute to cell invasion through secretion of cytokines and recently, IL-33/ST2 pathway has gained huge interest as a protumor alarmin, promoting progression to metastasis by inducing changes in TM. Hence, we analyzed IL-33 and ST2 content in tumor and healthy tissue lysates and plasma from CRC patients. Tissue localization and distribution of these molecules was evaluated by immunohistochemistry (using localization reference markers a-smooth muscle actin or alpha-SMA and E-cadherin), and clinical/histopathological information was obtained from CRC patients. In vitro experiments were conducted in primary cultures of CAFs and normal fibroblasts (NFs) isolated from tumor and healthy tissue taken from CRC patients. Additionally, migration and proliferation analysis were performed in HT29 and HCT116 cell lines. It was found that IL-33 content increases in left-sided CRC patients with lymphatic metastasis, with localization in tumor epithelia associated with abundant desmoplasia. Although ST2 content showed similarities between tumor and healthy tissue, a decreased immunoreactivity was observed in left-sided tumor stroma, associated to metastasis related factors (advanced stages, abundant desmoplasia, and presence of tumor budding). A principal component analysis (including stromal and epithelial IL-33/ST2 and alpha-SMA immunoreactivity with extent of desmoplasia) allowed us to distinguish clusters of low, intermediate and abundant desmoplasia, with potential to develop a diagnostic signature with benefits for further therapeutic targets. IL-33 transcript levels from CAFs directly correlated with CRC cell line migration induced by CAFs conditioned media, with rhlL-33 inducing a mesenchymal phenotype in HT29 cells. These results indicate a role of IL-33/ST2 in tumor microenvironment, specifically in the interaction between CAFs and epithelial tumor cells, thus contributing to invasion and metastasis in left-sided CRC, most likely by activating desmoplasia.
dc.fuente.origenWOS
dc.identifier.doi10.3389/fimmu.2019.01394
dc.identifier.issn1664-3224
dc.identifier.urihttps://doi.org/10.3389/fimmu.2019.01394
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/100949
dc.identifier.wosidWOS:000472468000002
dc.language.isoen
dc.revistaFrontiers in immunology
dc.rightsacceso restringido
dc.subjectcolorectal cancer
dc.subjectcancer associated fibroblasts
dc.subjectinterleukin 33
dc.subjectdesmoplasia
dc.subjectepithelial-mesenchymal transition
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleInterleukin 33/ST2 Axis Components Are Associated to Desmoplasia, a Metastasis-Related Factor in Colorectal Cancer
dc.typeartículo
dc.volumen10
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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