Abstract
Background. Increasing evidence argues that soluble CXCL16 promotes proliferation, migration, and invasion of cancer cells in vitro. However, the role of transmembrane or cellular CXCL16 in cancer remains relatively unknown. In this study, we determine the function of cellular CXCL16 as tumor suppressor in breast cancer cells. Methods. Expression of cellular CXCL16 in breast cancer cell lines was determined at both RNA and protein levels. In vitro and in vivo studies that overexpressed or downregulated CXCL16 were conducted in breast cancer cells. Results. We report differential expression of cellular CXCL16 in breast cancer cell lines that was negatively correlated with cell invasiveness and migration. Overexpression of CXCL16 in MDA-MB-231 cells led to a decrease in cell invasion and migration and induced apoptosis of the cells; downregulation of CXCL16 in MCF-7 cells increased cell migration and invasiveness. Consistent with the in vitro data, CXCL16 overexpression inhibited tumorigenesis in vivo. Conclusions. Cellular CXCL16 suppresses invasion and metastasis of breast cancer cells in vitro and inhibits tumorigenesis in vivo. Targeting of cellular CXCL16 expression is a potential therapeutic strategy for breast cancer.
Highlights
CXCL16, a newly identified chemokine, has been described in both transmembrane and soluble forms [1]
Expression of CXCL16 was evaluated in mammary epithelial cell MCF-10A and in three breast cancer cell lines: SKBR-3, MCF-7, and MDA-MB-231
Previous findings from in vitro studies using exogenous Soluble CXCL16 (sCXCL16) suggested that sCXCL16 promotes cell proliferation and invasion
Summary
CXCL16, a newly identified chemokine, has been described in both transmembrane and soluble forms [1]. Lu et al revealed a positive correlation between CXCL16 mRNA expression and prostate cancer aggressiveness such that metastatic lesions expressed higher levels of CXCL16 mRNA than the primary prostate tissues [9] These results suggest a role for CXCL16 in cancer aggressiveness. Expression of cellular CXCL16 in breast cancer cell lines was determined at both RNA and protein levels. In vitro and in vivo studies that overexpressed or downregulated CXCL16 were conducted in breast cancer cells. We report differential expression of cellular CXCL16 in breast cancer cell lines that was negatively correlated with cell invasiveness and migration. Cellular CXCL16 suppresses invasion and metastasis of breast cancer cells in vitro and inhibits tumorigenesis in vivo. Targeting of cellular CXCL16 expression is a potential therapeutic strategy for breast cancer
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