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Chemokine CXCL3 mediates prostate cancer cells proliferation, migration and gene expression changes in an autocrine/paracrine fashion.

AbstractINTRODUCTION:
We have previously indicated that CXCL3 was upregulated in the tissues of prostate cancer, and exogenous administration of CXCL3 played a predominant role in the tumorigenicity of prostate cancer cells. In the present study, we further explored the role and the underlying mechanism of CXCL3 overexpression in the oncogenic potential of prostate cancer in an autocrine/paracrine fashion.
METHODS:
CXCL3-overexpressing prostate cancer cell line PC-3 and immortalized prostate stromal cell line WPMY-1 were established by gene transfection. CCK-8, transwell assays and growth of tumor xenografts were conducted to characterize the effects of CXCL3 on PC-3 cells' proliferation and migration. Western blotting was conducted to test whether CXCL3 could affect the expression of tumorigenesis-associated genes.
RESULTS:
The results showed that CXCL3 overexpression in PC-3 cells and the PC-3 cells treated with the supernatants of CXCL3-transfected WPMY-1 cells stimulated the proliferation and migration of PC-3 cells in vitro and in a nude mouse xenograft model. Western blotting revealed higher levels of p-ERK, Akt and Bcl-2 and lower levels of Bax in the tumor xenografts transplanted with CXCL3-transfected PC-3 cells. Moreover, the tumor xenografts derived from the PC-3 cells treated with supernatants of CXCL3-transfected WPMY-1 cells showed higher expression of ERK, Akt and Bcl-2 and lower expression of Bax.
CONCLUSIONS:
These findings suggest that CXCL3 autocrine/paracrine pathways are involved in the development of prostate cancer by regulating the expression of the target genes that are related to the progression of malignancies.
AuthorsHua Xin, Yu Cao, Ming-Liang Shao, Wei Zhang, Chun-Bin Zhang, Jing-Tao Wang, Li-Chun Liang, Wen-Wu Shao, Ya-Ling Qi, Yue Li, Ze-Yu Zhang, Zhe Yang, Yu-Hong Sun, Peng-Xia Zhang, Lin-Lin Jia, Wei-Qun Wang
JournalInternational urology and nephrology (Int Urol Nephrol) Vol. 50 Issue 5 Pg. 861-868 (May 2018) ISSN: 1573-2584 [Electronic] Netherlands
PMID29524043 (Publication Type: Journal Article)
Chemical References
  • BAX protein, human
  • CXCL3 protein, human
  • Chemokines, CXC
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • bcl-2-Associated X Protein
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases
Topics
  • Animals
  • Autocrine Communication
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Chemokines, CXC (genetics, metabolism)
  • Extracellular Signal-Regulated MAP Kinases (genetics, metabolism)
  • Gene Expression
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Paracrine Communication
  • Phosphorylation
  • Prostate (cytology)
  • Prostatic Neoplasms (genetics, metabolism, pathology)
  • Proto-Oncogene Proteins c-akt (genetics, metabolism)
  • Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism)
  • RNA, Messenger (metabolism)
  • Stromal Cells
  • Transfection
  • bcl-2-Associated X Protein (genetics, metabolism)

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