CCL21/CCR7 enhances the proliferation, migration, and invasion of human bladder cancer T24 cells

  • PLoS One. 2015 Mar 23;10(3):e0119506. doi: 10.1371/journal.pone.0119506.
Miao Mo  1 ,  Mi Zhou  2 ,  Lu Wang  3 ,  Lin Qi  1 ,  Kehua Zhou  4 ,  Long-Fei Liu  1 ,  Zhi Chen  1 ,  Xiong-Bing Zu  1
Affiliations
  • 1. Department of Urology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, P.R. China.
  • 2. Department of Urology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.
  • 3. Health Management Center, Xiangya Hospital, Central South University, Changsha 410008, Hunan, P.R. China.
  • 4. Department of Health Care Studies, Daemen College, 4380 Main Street, Amherst, NY 14226, United States of America.
PMID: 25798926 DOI: 10.1371/journal.pone.0119506
Abstract

Objective: To investigate the effects of CCL21/CCR7 on the proliferation, migration, and invasion of T24 cells and the possible associated mechanisms: expression of MMP-2 and MMP-9, and regulation of Bcl-2 and Bax proteins.

Methods: T24 cells received corresponding treatments including vehicle control, antibody (20 ng/mL CCR7 antibody and 50 ng/ml CCL21), and 50, 100, and 200 ng/ml CCL21. Proliferation was evaluated by MTT assay; cell migration and invasion were assayed using a transwell chamber. Cell Apoptosis was induced by Adriamycin (ADM). The rate of cell Apoptosis was examined by flow cytometry using annexin V-FITC/PI staining. Western-blot was used to analyze MMP-2 and MMP-9 and Bcl-2 and Bax proteins.

Results: CCL21 promoted T24 cell proliferation in concentration-dependent manner with that 200 ng/mL induced the largest amount of proliferation. Significant differences of cell migration were found between CCL21treatment groups and the control group in both the migration and invasion studies (P < 0.001 for all). The expressions of MMP-2 and MMP-9 proteins were significantly increased after CCL21 treatment (p < 0.05 for all). Protein expression of Bcl-21 follows an ascending trend while the expression of Bax follows a descending trend as the concentration of CCL21 increases. No difference was found between the control group and antibody group for all assessments.

Conclusion: CCL21/CCR7 promoted T24 cell proliferation and enhanced its migration and invasion via the increased expression of MMP-2 and MMP-9. CCL21/CCR7 had antiapoptotic activities on T24 cells via regulation of Bcl-2 and Bax proteins. CCL21/CCR7 may promote Bladder Cancer development and metastasis.

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