Evidence map›Paper›PMID 32319605›Full record

ArticleInternational journal of oncology2020

ADAM17-regulated CX3CL1 expression produced by bone marrow endothelial cells promotes spinal metastasis from hepatocellular carcinoma.

Chi Sun, Annan Hu, Shengxing Wang, Bo Tian, Libo Jiang, Yun Liang, Houlei Wang, Jian Dong

Open access · hybridAbstract read
In one paragraph

Article in International journal of oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 1 pooled it
1.9field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.

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  7. Journal of Taibah University Medical Sciences · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 1 country.

Chi Sun *Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
Annan Hu *Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
Shengxing Wang *Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
Bo TianDepartment of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
Libo JiangDepartment of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
Yun LiangDepartment of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
Houlei WangDepartment of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
Jian DongDepartment of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
The First Affiliated Hospital, Sun Yat-sen University · CNZhongshan Hospital · CNFudan University · CNSun Yat-sen University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Spinal metastasis occurs in 50‑75% of bone metastases caused by hepatocellular carcinoma (HCC), and HCC‑derived spinal metastasis can lead to a less favorable prognosis. Recently, several studies have demonstrated that C‑X3‑C motif chemokine ligand 1 (CX3CL1) is closely associated with cancer metastasis, and its secretion is modulated by a disintegrin and metalloproteinase 17 (ADAM17). Bone marrow endothelial cells (BMECs) are an essential component of bone marrow. However, little is known about the roles in and effects of BMECs on HCC spinal metastasis. The present study demonstrated that CX3CL1 and C‑X‑C motif chemokine receptor 3 (CXCR3) expression was upregulated in HCC spinal metastases, and that CX3CL1 promoted the migration and invasion of HCC cells to the spine. Western blot analysis revealed that the Src/protein tyrosine kinase 2 (PTK2) axis participated in CX3CL1‑induced HCC cell invasion and migration. CX3CL1 also increased the expression of M2 macrophage markers in THP‑1 monocytes. BMECs promoted the migration and invasion of Hep3B and MHCC97H cells by secreting soluble CX3CL1, whereas the neutralization of CX3CL1 inhibited this enhancement. CX3CL1 enhanced the activation of the phosphatidylinositol‑4,5‑bisphosphate 3‑kinase catalytic subunit alpha (PIK3CA)/AKT serine/threonine kinase 1 (AKT1) and Ras homolog family member A (RHOA)/Rho associated coiled‑coil containing protein kinase 2 (ROCK2) signaling pathways through the Src/PTK2 signaling pathway. Furthermore, ADAM17 was activated by mitogen‑activated protein kinase (MAPK)z14 in BMECs and significantly promoted the secretion of CX3CL1. HCC cells enhanced the recruitment and proliferation of BMECs. The overexpression of CX3CR1 facilitated the spinal metastasis of HCC in a mouse model in vivo. In addition, in vivo experiments revealed that BMECs promoted the growth of HCC in the spine. The present study demonstrated that CX3CL1 participates in HCC spinal metastasis, and that BMECs play an important role in the regulation of CX3CL1 in the spinal metastatic environment.

Indexed as

ADAM17 ProteinAdultAgedAnimalsBone MarrowCarcinoma, HepatocellularCell Line, TumorCell MovementCell ProliferationChemokine CX3CL1Endothelial Progenitor CellsFocal Adhesion Kinase 1Gene Expression Regulation, NeoplasticGene Knockdown TechniquesHumansImidazolesADAM17 ProteinADAM17 protein, humanChemokine CX3CL1CX3CL1 protein, humanCXCR3 protein, humanFocal Adhesion Kinase 1ImidazolesMitogen-Activated Protein Kinase 14PTK2 protein, humanPyridinesReceptors, CXCR3RNA, Small InterferingSB 203580a disintegrin and metalloproteinase 17bone marrow endothelial cellsC-X3-C motif chemokine ligand 1hepatocellular carcinomaspinal metastasis

Identifiers

PMID32319605
PMCPMC7252465
OpenAlexW3016239782

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.