Dynamic stromal cellular reaction throughout human colorectal adenoma-carcinoma sequence: A role of TH17/IL-17A - 17/06/21
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Abstract |
Background |
Accumulating data suggest that the tumour stroma rapidly undergoes dynamic mechanical and cellular changes by which creates a supportive milieu to promote disease progression and metastasis. Cytokines are reported to play a key role in the modulation of tumour stromal response.
Methods |
The activation of TH17/interleukin (IL)−17A network in association with tumour stromal proliferative and cellular response in samples from 50 patients with colorectal adenoma, 45 with colorectal cancer (CRCs) were elucidated with quantitative real-time PCR (q-PCR), immunohistochemistry and double immunofluorescence.
Results |
q-PCR results showed that retinoic acid-receptor-related orphan receptor-C, a critical transcriptional factor for TH17 cell differentiation, was significantly increased at the adenoma stage and slightly decreased at the CRC stage, but was still higher than that at normal controls. The level of TH17 signature cytokine IL-17A was shown in an increasing gradient throughout the adenoma-carcinoma sequence. Immunohistochemistry revealed an activated proliferative rate evaluated by Ki67 and population expansion of myofibroblasts in the adenoma/CRC stroma. Notably, densities of IL-17A-expressing cells were associated with populations of Ki67-positive cells and myofibroblasts in the adenoma/CRC stroma. Finally, CD146-positive stromal cells are an important participator for stroma remodelling, double immunofluorescence image demonstrated that IL-17 receptor C, one of the key elements for IL-17 receptor complex, was highly expressed in CD146-positive adenoma/CRC stromal cells.
Conclusions |
An activated TH17/IL-17A network in the tumour microenvironment is significantly associated with dynamic stromal cellular response throughout the adenoma–carcinoma sequence, which might provide a supportive environment for the initiation and progression of CRC.
Le texte complet de cet article est disponible en PDF.Highlights |
• | The TH17/IL-17 network promotes the development of human colorectal cancer. |
• | An activated TH17/IL-17 network is associated with stromal cellular reaction and neoplastic transformation along the adenoma-carcinoma progression sequence. |
• | We further showed that one of the key elements for IL-17 receptor complex was highly expressed in CD146-positive stromal cells, suggested that a possible pathway for TH17/IL-17 in regulating stromal cellular response during the process of carcinogenesis is probably via an action on CD146-positive stromal cells. |
Abbreviations : CRC, CT, DIF, EMT, IHC, IL, IL-17RC, MSC, qPCR, ROR, TGF, TH, VEGFR2
Keywords : Stroma, TH17, Cytokine, Carcinogenesis, Colorectum
Plan
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