The Axin2-Snail axis promotes bone invasion by activating cancer-associated fibroblasts in oral squamous cell carcinoma
| Autor: | Junqi Ling, Eunae Cho, Yin-Zhe An, Xianglan Zhang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Adult Male Cancer Research Chemokine medicine.medical_treatment Snail lcsh:RC254-282 CCL5 03 medical and health sciences Mice 0302 clinical medicine Bone invasion Axin Protein Cancer-Associated Fibroblasts biology.animal Genetics medicine Animals Humans Interleukin 8 Cytokine Cancer-stroma crosstalk Aged Retrospective Studies Aged 80 and over biology CAFs Middle Aged Prognosis lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Desmoplasia stomatognathic diseases 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer cell Cancer research biology.protein Carcinoma Squamous Cell Axin2 Immunohistochemistry Female Mouth Neoplasms OSCC medicine.symptom Research Article |
| Zdroj: | BMC Cancer, Vol 20, Iss 1, Pp 1-11 (2020) BMC Cancer |
| DOI: | 10.21203/rs.3.rs-30648/v3 |
| Popis: | Background In bone-invasive oral squamous cell carcinoma (OSCC), cancer-associated fibroblasts (CAFs) infiltrate into bony tissue ahead of OSCC cells. In the present study, we aimed to investigate the role of the Axin2-Snail axis in the biological behaviour of CAFs and bone invasion in OSCC. Methods The clinicopathological significance of Axin2 and Snail expression was investigated by immunohistochemistry in an OSCC cohort containing 217 tissue samples from patients with long-term follow-up. The influence of the Axin2-Snail axis on the biological behaviour of OSCC cells and CAFs was further investigated both in vitro and in vivo. Results Axin2 expression was significantly associated with Snail expression, the desmoplasia status, and bone invasion in patients with OSCC. In multivariate analysis, lymph node metastasis, desmoplasia, Axin2 expression, and Snail expression were independent poor prognostic factors in our cohort. Consistent with these findings, OSCC cells demonstrated attenuated oncogenic activity as well as decreased expression of Snail and various cytokines after Axin2 knockdown in vitro. Among the related cytokines, C-C motif chemokine ligand 5 (CCL5) and interleukin 8 (IL8) demonstrated a strong influence on the biological behaviour of CAFs in vitro. Moreover, both the desmoplastic reaction and osteolytic lesions in the calvaria were predominantly decreased after Axin2 knockdown in OSCC cells in vivo using a BALB/c athymic nude mouse xenograft model. Conclusions Oncogenic activities of the Axin2-Snail axis are not limited to the cancer cells themselves but rather extend to CAFs via regulation of the cytokine-mediated cancer-stromal interaction, with further implications for bone invasion as well as a poor prognosis in OSCC. |
| Databáze: | OpenAIRE |
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