In:
Cancer Science, Wiley, Vol. 109, No. 3 ( 2018-03), p. 710-723
Abstract:
In the hepatocellular carcinoma ( HCC ) microenvironment, chemokine receptors play a critical role in tumorigenesis and metastasis. Our previous studies have found that osteopontin ( OPN ) is a promoter for HCC metastasis. However, the role of chemokine receptors in OPN ‐induced HCC metastasis remains unclear. In this study, we demonstrate that OPN is dramatically elevated in HCC tissues with metastasis and that high expression of OPN correlates with poorer overall survival and higher recurrence rate. OPN upregulates chemokine receptor expression, migration, invasion and pulmonary metastasis in HCC . We find that C‐C chemokine receptor type 1 ( CCR 1) and C‐X‐C chemokine receptor type 6 ( CXCR 6) are the most upregulated chemokine receptors induced by OPN . CCR 1 knockdown results in reduction of migration, invasion and pulmonary metastasis induced by OPN in vitro and in vivo, whereas CXCR 6 knockdown does not reverse OPN ‐promoted migration and invasion. Moreover, OPN upregulates the expression of CCR 1 through activating phosphoinositide 3‐kinase ( PI 3K)/ AKT and hypoxia‐inducible factor 1α ( HIF ‐1α) in HCC cells. Furthermore, blockade of OPN ‐ CCR 1 axis with CCR 1 antagonist significantly restrains the promoting effects of OPN on HCC progression and metastasis. In human HCC tissues, OPN expression shows significantly positive correlation with CCR 1 expression, and the patients with high levels of both OPN and CCR 1 have the most dismal prognosis. Collectively, our results indicate that the OPN ‐ CCR 1 axis in HCC is important for accelerating tumor metastasis and that CCR 1 is a potential therapeutic target for controlling metastasis in HCC patients with high OPN .
Type of Medium:
Online Resource
ISSN:
1347-9032
,
1349-7006
DOI:
10.1111/cas.2018.109.issue-3
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
2115647-5
detail.hit.zdb_id:
2111204-6
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