Chemokine CXCL16 Expression Suppresses Migration and Invasiveness and Induces Apoptosis in Breast Cancer Cells

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.

Scavenger Receptors

“…Immunohistochemistry and flow cytometry analyses showed that SR-PSOX/CXCL16 was located predominantly in the membrane and cytosol of RCC cell lines (Gutwein et al, 2009). In line with these clinical data, overexpression of TM-CXCL16 in breast cancer MDA-MB-231 cells suppressed their invasiveness in vitro and tumorigenesis in vivo (Fang et al, 2014). IR can upregulate the expression of TM-CXCL16 and promote the shedding of sCXCL16, which results in improved therapeutic efficacy by recruiting CD8 + CXCR6 + effector T cells (Matsumura & Demaria, 2010; Matsumura et al, 2008).…”

Soluble CXCL16 promotes TNF‐α‐induced apoptosis in DLBCL via the AMAD10‐NF‐κB regulatory feedback loop

“…The expression and role of CXCL16 in human malignancies have received increasing attention. Abnormal expression of CXCL16 was detected in various cancers, such as colorectal cancer (Kee et al, 2013), breast cancer (Fang et al, 2014), non-small-cell lung cancer (Liang et al, 2018), pancreatic cancer (Wente et al, 2008), and nasopharyngeal carcinoma (Zhu et al, 2015). The effects of CXCL16 in contributing to the malignancy of tumors seem to be dependent on tumor type.…”

LNA aptamer based multi-modal, Fe 3 O 4 -saturated lactoferrin (Fe 3 O 4 -bLf) nanocarriers for triple positive (EpCAM, CD133, CD44) colon tumor targeting and NIR, MRI and CT imaging

“…The role of CXCL16 in cancer is quite unclear, while studies claim that it acts as a regulator in metastasis and progression of cancer, studies have also shown that it suppresses migration and invasion by attracting CD8 lymphocytes to tumor and leads to induction of apoptosis [42,43]. Although an insignificant decrease in expression of FGF (acidic) was observed, it is known that FGF induces mitogenic and cell survival activities including cell growth, morphogenesis, tissue repair, tumor growth and invasion [44].…”