Abstract
Cancer progression involves carcinogenesis, an increase in tumour size, and metastasis. Here, we investigated the effect of overexpressed CXC chemokine ligand 14 (CXCL14) on these processes by using CXCL14/BRAK (CXCL14) transgenic (Tg) mice. The rate of AOM/DSS-induced colorectal carcinogenesis in these mice was significantly lower compared with that for isogenic wild type C57BL/6 (Wt) mice. When tumour cells were injected into these mice, the size of the tumours that developed and the number of metastatic nodules in the lungs of the animals were always significantly lower in the Tg mice than in the Wt ones. Injection of anti-asialo-GM1 antibodies to the mice before and after injection of tumour cells attenuated the suppressing effects of CXCL14 on the tumor growth and metastasis, suggesting that NK cell activity played an important role during CXCL14-mediated suppression of tumour growth and metastasis. The importance of NK cells on the metastasis was also supported when CXCL14 was expressed in B16 melanoma cells. Further, the survival rates after tumour cell injection were significantly increased for the Tg mice. As these Tg mice showed no obvious abnormality, we propose that CXCL14 to be a promising molecular target for cancer suppression/prevention.
Highlights
Suppressed rate of carcinogenesis and decreases in tumour volume and lung metastasis in CXC chemokine ligand 14 (CXCL14)/breast and kidney expressed chemokine (BRAK) transgenic mice
Sections obtained from the distal colon taken at 56 days showed an obvious decrease in the number of carcinogenic foci, which were composed of fused glands with enlarged hyperchromatic nuclei, in the Tg compared with that in the wild type C57BL/6 (Wt) (Fig. 1d)
In order to investigate the effect of CXCL14 overexpression on the processes of carcinogenesis, increase in tumour volume, and metastasis, we utilized three lines of Tg mice, all of which ubiquitously express approximately 10-fold more CXCL14 than normal Wt mice[21]
Summary
Suppressed rate of carcinogenesis and decreases in tumour volume and lung metastasis in CXCL14/BRAK transgenic mice. An increase in tumour size, and metastasis. The survival rates after tumour cell injection were significantly increased for the Tg mice. As these Tg mice showed no obvious abnormality, we propose that CXCL14 to be a promising molecular target for cancer suppression/prevention. Chemokine expression acts to determine the distribution of immune cells, and it controls the overall immune response to the tumour, and plays an integral role in the regulation of cancer progression and metastasis[13,14,15,16]
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