Foxp3+IL-17+ T cells promote development of cancer-initiating cells in colorectal cancer.
The pathogenesis of CRC remains to be further understood. This study was designed to elucidate the role of Foxp3+IL-17+ T cells in the pathogenesis of CRC. Surgically removed CRC tissue was collected from 12 patients with CRC. The frequency and cytokine profile of Foxp3+IL-17+ T cells in CRC were examined by flow cytometry. Chemokine CXCL11 was examined in CRC tissue by Western blotting. Treg chemotaxis was examined in a transwell system. The effect of Foxp3+IL-17+ T cells on induction of cancer-initiating cells was examined; the latter's Akt and MAPK activities and colony formation were examined afterward. Abundant Foxp3+IL-17+ T cells were detected in CRC tissue that expresses high levels of TGF-β, CXCR3, CCR6, and RORγt. High levels of CXCL11 were detected in CRC tissue-derived CD68+ cells, which had a strong chemotactic effect on Foxp3+ Tregs. Hypoxia induced the expression of IL-17 in Foxp3+ Tregs; Foxp3+IL-17+ T cells were capable of inducing CRC-associated cell markers in BMMo and drove the cells to be cancer-initiating cells. High levels of phosphorylated Akt and MAPK were detected in the induced cancer-initiation cells; the latter has the capability to form a colony. CRC tissue-derived Foxp3+IL-17+ cells have the capacity to induce cancer-initiating cells.
Yang
Shaobo
S
Department of Gastroenterology (South Building), China PLA General Hospital, Beijing, China.
Wang
Binquan
B
Guan
Chunying
C
Wu
Benyan
B
Cai
Changhao
C
Wang
Mengwei
M
Zhang
Binsheng
B
Liu
Tao
T
Yang
Pingchang
P
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D015687:Cell Hypoxia; D054371:Chemokine CXCL11 / Q000378:metabolism; D002633:Chemotaxis; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology*; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000276:immunology* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D014408:Biomarkers, Tumor; D054371:Chemokine CXCL11; D051858:Forkhead Transcription Factors; D020381:Interleukin-17; D020928:Mitogen-Activated Protein Kinases; D051057:Proto-Oncogene Proteins c-akt; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C515202:CXCL11 protein, human; C418974:FOXP3 protein, human