Expression of the chemokine receptor CCR6 in the Lewis lung carcinoma (LLC) cell line reduces its metastatic potential in vivo

Abstract

Chemokines and their receptors play important roles in various aspects of tumoral processes, and evidence was provided for their critical involvement in determining the metastatic destination of tumor cells. Here, we analyzed in vitro and in vivo, how CCR6 expression could alter the behavior of Lewis lung carcinoma (LLC) cells, which were shown to express low levels of the CCR6 ligand, CCL20 (LARC), both in vitro and in vivo. The expression of CCR6 significantly decreased the number of metastases in immunocompetent C57BL/6 mice, without affecting the tumor-forming ability of LLC cells. This was correlated with a decrease in clonogenicity in soft and hard agar, and with increased adhesion to type-IV collagen. These two observations made in basal conditions were enhanced when CCL20 was added to the assay medium. Thus, expression of CCR6 in tumor cells, associated with the local production of CCL20, decreased the metastatic potential of the LLC line. We propose a model, in which the expression of a chemokine receptor in tumor cells can act as a metastasis-suppressor, or a metastasis-promoting factor, according to the expression, or the absence of expression of the cognate ligand(s) in the tumor.

Expression of the chemokine receptor CCR6 correlates with a favorable prognosis in patients with adenocarcinoma of the lung

“…The high magnification photograph (c) shows that CCR6 mainly localizes to the plasma membrane of the tumor cells. Normal epithelial cells do not express CCR6, but alveolar macrophages do (d) production of CCL20 in the lung and reduces the metastatic potential in mice [13]. The reason for the variation in the aforementioned results is not clear at this point.…”

“…CCR6 expression is reportedly related to liver metastasis [4,5], carcinogenesis, progression, and aggressiveness [6,7], and upregulated CCR6 expression is associated with poor prognosis in hepatocellular carcinoma [8][9][10]. On the other hand, downregulation of CCR6 is reportedly related to metastasis, both in vitro and in vivo [11][12][13]. At present, little is known about the effect of tumoral expression of CCR6 in NSCLC.…”

Loss of Circulating Mucosal-Associated Invariant T Cells in Common Variable Immunodeficiency Is Associated with Immune Activation and Loss of Eomes and PLZF

“…A possible explanation for the low levels of MAIT cells in the blood is their recruitment to tissues. The lower levels of the chemokine receptor CCR6 we observed on MAIT cells in CVID patients may possibly represent internalization of this receptor following interaction with its ligand MIP-3 (43). In HIV-infected subjects, the levels of IL-7 are associated with MAIT cell frequency (39).…”

“…Interestingly, all CVID patients with MAIT cell frequency within the normal range had undetectable MIP-3, whereas all those with detectable MIP-3 had a low frequency of MAIT cells. Furthermore, it is possible that the low levels of CCR6 on MAIT cells may result from internalization of CCR6 following binding of its ligand (43). However, some CVID patients had a low frequency of circulating MAIT cells but undetectable MIP-3 levels, suggesting that other mechanisms are also contributing to the reduced frequency of peripheral MAIT cells.…”

Viral Anti-Inflammatory Proteins: The Potential for Immunotherapeutic Applications in Cancer

“…Research has uncovered extensive interactions between tumor cells and the surrounding microenvironment [1][2][3][4][5][6][7][8][9][10]. Cancer cells modulate the local cellular responses to provide support for their growth, invasion and even metastases.…”