CX3CL1: a potential chemokine widely involved in the process spinal metastases

Liu, Wangmi; Bian, Chong; Liang, Yun; Jiang, Libo; Chen, Qian; Dong, Jian

doi:10.18632/oncotarget.14773

Cited by 25 publications

(20 citation statements)

References 24 publications

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“…However, recent research has demonstrated that the CX3CL1/CX3CR1 axis is involved in the survival, adhesion, and migration of malignant tumor cells, including breast cancer 13 , 14 . In our previous research, we first demonstrated that CX3CL1 was associated with the process of spinal metastases from different malignant primary tumors, including breast cancer 15 . Unfortunately, the molecular mechanism of breast cancer metastasizing to the spine still remains poorly understood.…”

Section: Introductionmentioning

confidence: 99%

CX3CL1 involves in breast cancer metastasizing to the spine via the Src/FAK signaling pathway

Liang¹,

Lee²,

Liu³

et al. 2018

J. Cancer

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C-X3-C chemokine ligand 1 (CX3CL1) has been shown to be involved in the development of multiple tumors. Our previous study demonstrated that CX3CL1 may be involved in the process of metastasis of various malignant tumors to the spine, including breast cancer, but the molecular mechanism was still unknown. In the present study, we found that the receptor CX3CR1 was overexpressed in the spinal metastases of breast cancer than in para-tumor tissue. In terms of CX3CL1, it was significantly more expressed in normal spinal cancellous bone than in limbs. However, CX3CR1 was not expressed at a high level in every breast cancer cell compared with the human mammary epithelial cell line MCF-10A. In addition, CX3CL1 did promote the migration and invasion abilities of MDA-MB-231 cells. However, CX3CL1 has no obvious effect on cell growth. Furthermore, CX3CL1 induced chemotaxis of tumor cells via the Src/FAK signaling pathway. The migration index enhanced by CX3CL1 was dramatically declined using Bosutinib and PF-00562271, which are the inhibitors of Src and FAK signaling pathways, respectively. Therefore, CX3CL1 in spinal cancellous bone attracts CX3CR1-expressing tumor cells to the spine and enhances their migration and invasion abilities through the Src/FAK signaling pathway.

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Section: Introductionmentioning

confidence: 99%

CX3CL1 involves in breast cancer metastasizing to the spine via the Src/FAK signaling pathway

Liang¹,

Lee²,

Liu³

et al. 2018

J. Cancer

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“…CX3CL1 is involved in the invasion and metastasis of various malignant tumor types and promotes tumor metastasis via chemotaxis and adhesion of circulating tumor cells (Tardáguila et al, 2013;Liu et al, 2016). Our previous study found that CX3CL1 was highly expressed in spinal osseous tissues compared with limb osseous tissues, and the patients with spinal metastases exhibited high levels of CX3CL1 (Liu et al, 2017). The above results suggested that CX3CL1 serves essential roles in tumor cell metastasis to the spine.…”

Section: Discussionmentioning

confidence: 82%

“…Vertebral cancellous bones, as a preferential district for bone metastases, are highly efficient at arresting circulating cancer cells from low-velocity bloodstream. Furthermore, CX3CL1, which is rich in vertebral microenvironments (Liu et al, 2017), chemo-attracts many tumor cells from blood circulation to the spine. CX3CL1 functions as an adhesion molecule for arresting circulating tumor cells in spine microvasculature (Ostuni et al, 2014;Zhou et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

CX3CL1 Induces Vertebral Microvascular Barrier Dysfunction via the Src/P115-RhoGEF/ROCK Signaling Pathway

Lee

Liang

Zhao

et al. 2020

Front. Cell. Neurosci.

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Trans-endothelial migration (TEM) of cancer cells is a critical step in metastasis. Micro-vascular barrier disruptions of distant organs play important roles in tumor cells TEM. The spine is a preferred site for multiple cancer cell metastases. Our previous study found that vertebral spongy bone was rich in CX3CL1 and that CX3CL1 can attract fractalkine receptor-expressing tumor cells to the spine. In the present study, we determined whether CX3CL1 was involved in vertebral micro-vascular barrier disruption and promoted tumor cell TEM after circulating tumor cells were arrested in the vertebral micro-vasculature. We examined the role of CX3CL1 in the barrier function of vertebral micro-vascular endothelial cells (VMECs) and explored the molecular mechanisms of CX3CL1-induced VMEC barrier disruption. Our results demonstrated that CX3CL1 led to F-actin formation and ZO-1 disruption in VMECs and induced the vertebral micro-vascular barrier disruption. Importantly, we found that the activation of the Src/P115-RhoGEF/ROCK signaling pathway plays an important role in CX3CL1-induced VMEC stress fiber formation, ZO-1 disruption and then vertebral micro-vascular barrier hyper-permeability. Inhibiting Src/P115-RhoGEF/ROCK signaling in VMECs effectively blocked CX3CL1-induced vertebral vascular endothelial dysfunction and subsequent tumor cell TEM. The results of this study and our previous study indicate that in addition to its chemotaxis, CX3CL1 plays a critical role in regulating vertebral micro-vascular barrier function and tumor cell TEM. CX3CL1 induced VMECs stress fiber formation, ZO-1 disruption and then vascular endothelial hyperpermeability via activation of the Src/P115-RhoGEF/ROCK signaling pathway. The inhibition of the Src/P115-RhoGEF/ROCK signaling pathway in VMECs effectively blocked tumor cells TEMs in vertebral spongy bone and maybe a potential therapeutic strategy for spine metastases in the future.

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“…Inverse associations between the level of circulating CX3CL1 and risk of cancer on other sites have also been reported . At the same time, observations point to possible involvement of CX3CL1 in the development of spinal metastases in several cancers, including prostate cancer . Our observations may reflect a possible role of CX3CL1 in antitumor immunity against prostate cancer.…”

Section: Discussionmentioning

confidence: 99%

Circulating inflammation markers and prostate cancer

et al. 2019

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Background Chronic inflammation is thought to influence the risk of prostate cancer. The purpose of this population‐based case‐control study was to evaluate the association of 48 circulating inflammation markers with prostate cancer, to identify candidate markers for further investigation. Methods Serum samples collected from 235 prostate cancer patients and 198 population‐based controls recruited in Örebro County, Sweden, in 1989‐1991, were assessed using a multiplex bead‐based immunoassay to determine concentrations of 48 circulating inflammation markers. Logistic regression was first used to evaluate the association between individual markers (highest vs lowest concentration quartile) and prostate cancer in unadjusted and mutually adjusted models. Second, patients with inflammatory conditions, metastatic or advanced prostate cancer, were excluded to address the possible influence of systemic disease on inflammation markers. Results Individual analyses first identified 21 markers associated with prostate cancer (P < .05), which after mutual adjustment were reduced to seven markers. After the exclusion of men with conditions linked with systemic inflammation, associations between prostate cancer and deviant levels of C‐X3‐C motif chemokine ligand 1, platelet‐derived growth factor subunit B homodimer, interleukin 10, C‐C motif chemokine ligand (CCL) 21, and CCL11 remained statistically significant. Conclusions In this explorative study, we identified candidate inflammation markers of possible importance for prostate cancer pathophysiology, for further evaluation in prospective studies.

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CX3CL1: a potential chemokine widely involved in the process spinal metastases

Cited by 25 publications

References 24 publications

CX3CL1 involves in breast cancer metastasizing to the spine via the Src/FAK signaling pathway

CX3CL1 involves in breast cancer metastasizing to the spine via the Src/FAK signaling pathway

CX3CL1 Induces Vertebral Microvascular Barrier Dysfunction via the Src/P115-RhoGEF/ROCK Signaling Pathway

Circulating inflammation markers and prostate cancer

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