Suppressed rate of carcinogenesis and decreases in tumour volume and lung metastasis in CXCL14/BRAK transgenic mice

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.

CXCL14 suppresses human papillomavirus-associated head and neck cancer through antigen-specific CD8+ T-cell responses by upregulating MHC-I expression

“…CXCL14 may also induce tumor suppression in other cancers beyond HPV-positive cancers, as CXCL14 expression is downregulated in several cancers including renal and gastric cancers [18,19]. Indeed, restoration of CXCL14 expression triggers tumor suppression in lung and colorectal cancers, as well as HNC [44,48,49]. In addition, CXCL14 could be used to treat HPV-positive premalignant lesions for cancer prevention.…”

HIC1 deletion promotes breast cancer progression by activating tumor cell/fibroblast crosstalk

“…However, the effect of CXCL14 on cancer development remains controversial. Some reports have claimed antitumor and antiangiogenic effects of CXCL14 (47,48), whereas others noted upregulated expression of CXCL14 in several cancer types, including BrCa and osteosarcoma (49,50). A recent study also showed that CXCL14 expression in high stromal tissue, but not in epithelial tissue, is significantly associated with shorter survival in BrCa patients (51), raising the possibility that stromal CXCL14 may exert a procancer role in BrCa progression (52 vey the changes in 102 cytokines and chemokines in CM obtained from NAF10, CXCL14-activated NAF10, and CAF10 cells.…”

Adaptation to chronic acidic extracellular pH elicits a sustained increase in lung cancer cell invasion and metastasis

“…LLCm1 and LLCm1A cells were harvested with trypsin/ EDTA, resuspended in DMEM/F12 (pH 7.4) containing 10% FBS, and incubated at 37 °C for 1 h. The cells were washed twice with Mg 2+ and Ca 2+ -free phosphate-buffered saline (PBS(-)) and resuspended in ice cold PBS(-). In experimental metastasis assays [12,25,26], 3 × 10 5 cells in 200 µl PBS(-) were injected into the tail vein of each 7-week-old male C57BL/6 mouse (Clea Japan, Tokyo, Japan). Each experimental group consisting of 6 mice was housed in a cage.…”