Chemokine CXCL12 and its receptor CXCR4 expression are associated with perineural invasion of prostate cancer.
OBJECTIVE
To identify the roles of CXCL12 and CXCR4 and the associated mechanism involved in perineural invasion of prostate cancer.


METHODS
The distribution and expression of CXCL12, CXCR4, MMP-2 and MMP-9 in human prostate cancer and in tumor cells invading nerve tissue were studied with immunohistochemical staining. The effects of exogenous CXCL12 and CXCR4 antagonist AMD3100 on PC3 prostate cancer cells invasiveness were assessed in vitro and in vivo.


RESULTS
The expression of CXCL12, CXCR4, MMP-2, and MMP-9 in human prostate cancer were higher than those in hyperplastic prostate tissues (P < 0.05). In vitro CXCL12 could stimulate the PC3 cells invasiveness (P < 0.05) while AMD3100 could inhibit invasiveness. In vivo, the number of nerves around the tumor tissue in the group treated with CXCL12 was significantly higher than that found in the control group (P < 0.05). Both the control group and the CXCL12-treated group had more nerves number near the tumor tissue than it found in the AMD3100-treated group. The positive cell number of CXCL12, CXCR4, MMP-2, MMP-9, and NGF expression ranked from highest to lowest, were the CXCL12-treated, the control, and the AMD3100-treated group(P < 0.05).


CONCLUSIONS
CXCL12 and its receptor CXCR4 along with MMP-2 and MMP-9 are related with prostate cancer perineural invasion.
Zhang
Shiwu
S
Department of Pathology, Tianjin Cancer Hospital, Tianjin Medical University, Tianjin 300060, PR China. zhangshiwu666@yahoo.com.cn
Qi
Lisha
L
Li
Man
M
Zhang
Danfang
D
Xu
Shaoyan
S
Wang
Ning
N
Sun
Baocun
B
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D054377:Chemokine CXCL12 / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D009361:Neoplasm Invasiveness; D009412:Nerve Fibers / Q000473:pathology*; D020932:Nerve Growth Factor / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D019718:Receptors, CXCR4 / Q000378:metabolism*
D054377:Chemokine CXCL12; D019718:Receptors, CXCR4; D020932:Nerve Growth Factor; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9