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OncoTargets and Therapy Volume 13, 2020 - Issue
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Original Research

The Role of CCL20-CCR6 Axis in Ovarian Cancer Metastasis

Wan Liu1 Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai200127, People’s Republic of China;2 Shanghai Key Laboratory of Gynecologic Oncology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai200127, People’s Republic of ChinaORCID Iconhttps://orcid.org/0000-0002-4276-0062
ORCID Icon,
Wenjing Wang1 Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai200127, People’s Republic of China;2 Shanghai Key Laboratory of Gynecologic Oncology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai200127, People’s Republic of China
,
Ning Zhang1 Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai200127, People’s Republic of China;2 Shanghai Key Laboratory of Gynecologic Oncology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai200127, People’s Republic of China
&
Wen Di1 Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai200127, People’s Republic of China;2 Shanghai Key Laboratory of Gynecologic Oncology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai200127, People’s Republic of China;3 State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai200127, People’s Republic of ChinaCorrespondence[email protected] [email protected]
Pages 12739-12750 | Published online: 11 Dec 2020

Figures & data

Figure 1 CCL20 treatment selectively promotes ovarian cancer cell migration and invasion.

Notes: (A) Migration of ovarian cancer cells treated with rhCCL20 (20 ng/mL). (B) Invasion of ovarian cancer cells treated with rhCCL20 (20 ng/mL). (C) Proliferation of ovarian cancer cells treated with increasing concentrations of rhCCL20 (0.5, 1, 2, 4, 8, 16, 32, 64 ng/mL). *Compared to A2780 CTRL group, P<0.05; **Compared to SKOV3 CTRL group, P<0.05
Abbreviations: rhCCL20, recombinant human CCL20 protein; CTRL, control.
Figure 1 CCL20 treatment selectively promotes ovarian cancer cell migration and invasion.

Figure 2 CCR6 expression in ovarian cancer cell lines.

Notes: (A) mRNA expression of CCR6 in human ovarian epithelial cell line IOSE and ovarian cancer cell lines. (B) Protein expression of CCR6 in IOSE and ovarian cancer cells. *Compared to IOSE, P<0.05
Figure 2 CCR6 expression in ovarian cancer cell lines.

Figure 3 Knockdown of CCR6 inhibits CCL20-mediated migration and invasion of ovarian cancer cells.

Notes: (A) Migration of ovarian cancer cells transfected with siRNAs and treated with rhCCL20. (B) Invasion of ovarian cancer cells transfected with siRNAs and treated with rhCCL20. *Compared to NC group, P<0.05
Abbreviations: NC, negative control; rhCCL20, recombinant human CCL20 protein.
Figure 3 Knockdown of CCR6 inhibits CCL20-mediated migration and invasion of ovarian cancer cells.

Figure 4 Knockout of CCR6 inhibits CCL20-mediated migration and invasion of ovarian cancer cells.

Notes: (A) Protein expression of CCR6 in A2780 monoclonal cells transfected with sgCCR6 lentivirus. (B) The effect of CCR6 knockout on proliferation of A2780 cells. (C) The effect of CCR6 knockout on CCL20-induced cell migration and invasion. *Compared to NC group, P<0.05
Abbreviations: KO, knock-out; NC, negative control; rhCCL20, recombinant human CCL20 protein.
Figure 4 Knockout of CCR6 inhibits CCL20-mediated migration and invasion of ovarian cancer cells.

Figure 5 CCL20-CCR6 axis promotes ovarian cancer metastasis in vivo.

Notes: (A) Body weight of nude mice throughout the experiment. (B) The abdominal metastasis of ovarian cancer in nude mice. (C) Tumors dissected out from the abdominal cavity of nude mice. (D) The number of tumors dissected out from the abdominal cavity of nude mice. (E) The weight of tumors dissected out from the abdominal cavity of nude mice. *Compared to WT-PBS group, P<0.05; Yellow arrows, the abdominal metastatic ovarian tumors.
Abbreviations: WT, wild type; KO, knock-out; rhCCL20, recombinant human CCL20 protein.
Figure 5 CCL20-CCR6 axis promotes ovarian cancer metastasis in vivo.

Figure 6 Differentially expressed genes after rhCCL20 treatment in ovarian cancer cells.

Notes: (A) Heatmap of differentially expressed genes after rhCCL20 treatment in SKOV3 cells for 24 hours. (B) KEGG analysis of differentially expressed genes after rhCCL20 treatment. (C, D) qRT-PCR verification of the expression of VCAN, CDH1 and CDH2 in SKOV3 and A2780 cells after rhCCL20 treatment. (E) H&E staining and IHC staining of N-cadherin, E-cadherin and versican on tumor tissues from in vivo experiment. *Compared to CTRL group, P<0.05
Abbreviations: KEGG, Kyoto Encyclopedia of Genes and Genomes; CTRL, control; H&E, hematoxylin and eosin; IHC, immunohistochemical; rhCCL20, recombinant human CCL20 protein.
Figure 6 Differentially expressed genes after rhCCL20 treatment in ovarian cancer cells.

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