CXCR4/SDF-1 axis is involved in lymph node metastasis of gastric carcinoma

Zhao, Bi; Wang, Zhenjun; Mao, Weizheng; Ma, Huachong; Han, Jiagang; Zhao, Bo; Xu, Huimin

doi:10.3748/wjg.v17.i19.2389

Cited by 65 publications

(58 citation statements)

References 34 publications

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“…Overexpression of CXCR4 in gastric cancer cells was associated with the development of peritoneal carcinomatosis, which is induced by dissemination of cancer cells into the peritoneal cavity (20,24). Numerous studies have demonstrated that strong expression of CXCR4 is correlated with aggressive tumor characteristics such as deep invasion, lymph node, and liver metastasis (4,20,(25)(26)(27)(28). Furthermore, several pre-clinical investigations demonstrated that blocking of CXCR4 signaling reduced the size and number of tumor metastases (20,29,30).…”

Section: Discussionmentioning

confidence: 99%

Hypoxia induces CXCR4 expression and biological activity in gastric cancer cells through activation of hypoxia-inducible factor-1α

Kim

Song

et al. 2012

Oncology Reports

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Abstract. Given the important role of CXCR4 in cancer metastasis, microenvironmental factors that modulate CXCR4 may have an impact on the process of tumor expansion. Hypoxia is a common feature of solid tumors and a significant microenvironmental factor that drives aggressive behavior. CXCR4 is upregulated in several cancer cells under hypoxic conditions, suggesting a relationship between tumor hypoxia and CXCR4. However, the role of hypoxia in regulating CXCR4 in gastric cancer remains poorly understood. KATO III gastric cancer cells were exposed to hypoxia or normoxia. CXCR4 expression in cells transfected with shRNA specific for HIF-1α was investigated by western blotting and flow cytometry. Wound healing, migration and invasion assays were used to assess cell motility and the chemotactic response to CXCL12, a major CXCR4 ligand. CXCR4 expression at the protein level and in the cell membrane was significantly increased in KATO III cells following exposure to hypoxia. This upregulation of CXCR4 was implicated in increased cell motility and enhanced chemotactic responses (migration and invasion) to CXCL12 treatment in vitro. The increases in CXCR4 expression and metastatic potential in gastric cancer cells exposed to hypoxia were blocked by HIF-1α-specific shRNA. Our results indicate that hypoxia upregulates CXCR4 in gastric cancer cells in a HIF-1α-dependent manner, and that upregulation of CXCR4 plays a role in cancer cell migration and invasion. Thus, disrupting the hypoxia-HIF-1α-CXCR4 axis could be an attractive therapeutic strategy for the treatment of gastric cancer.

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Section: Discussionmentioning

confidence: 99%

Hypoxia induces CXCR4 expression and biological activity in gastric cancer cells through activation of hypoxia-inducible factor-1α

Kim

Song

et al. 2012

Oncology Reports

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“…Our previous investigation showed that the human gastric cancer cells SGC-7901 expressed CXCR4, while UCBMSCs expressed stromal derived factor-1 (SDF-1). The interaction between these two molecules induced the MSCs to migrate into gastric tumor tissues [32]. Nakamizo et al [7] reported that BM-MSCs have a tropism for brain tumors and thus could be used as delivery vehicles for glioma therapy, and BM-MSCs were seen exclusively within the brain tumors regardless of whether the cells were injected into the ipsilateral or contralateral carotid artery.…”

Section: Discussionmentioning

confidence: 99%

Gene therapy of gastric cancer using LIGHT-secreting human umbilical cord blood-derived mesenchymal stem cells

Zhu

Xuan

et al. 2012

Gastric Cancer

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Background Mesenchymal stem cells (MSCs) have the ability to migrate into tumors and therefore are potential vehicles for the therapy of malignant diseases. In this study, we investigated the use of umbilical cord blood mesenchymal stem cells (UCB-MSCs) as carriers for a constant source of transgenic LIGHT (TNFSF14) to target tumor cells in vivo.Methods Lentiviral vectors carrying LIGHT genes were constructed, producing viral particles with a titer of 2 9 10 8 TU/L. Fourteen days after UCB-MSCs transfected by LIGHT gene packaged lentivirus had been injected into mouse gastric cancer models, the expression levels of LIGHT mRNA and protein were detected by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Then the tumors' approximate volumes were measured. Results The treatment with MSC-LIGHT demonstrated a strong suppressive effect on tumor growth compared to treatment with MSC and NaCl (p \ 0.001). Examination of pathological sections of the tumor tissues showed that the areas of tumor necrocis in the MSC-LIGHT group were larger than those in the MSC group. Moreover, we found that MSCs with LIGHT were able to significantly induce apoptosis of tumor cells. The expression levels of LIGHT mRNA and protein were significantly higher in the UCBMSCs with the LIGHT gene than the levels in UCB-MSCs (p \ 0.001). Conclusion These results suggest that UCB-MSCs carrying the LIGHT gene have the potential to be used as effective delivery vehicles in the treatment of gastric cancers.

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“…When they screened 40 gastric cancer patient samples, Zhao et al [124] found that CXCR4 mRNA levels were significantly higher in cases with lymph node metastasis than those without; they also found that the CXCR4 protein level was correlated with poorly differentiated lesions, more advanced tumor stage and lymph node metastasis. Further, they reported higher CXCL12 mRNA in lymph nodes in patients with metastatic gastric cancer.…”

Section: Stomachmentioning

confidence: 99%

“…Positive regulator of HER [116] Stomach CXCL12, CXCR4 Metastasis through activation of AKT-mTOR pathway and MMPs, upregulation in lymph node metastasis, strong correlation with tumor development [117,118,124] …”

Section: Cxcr4mentioning

confidence: 99%

Chemokines, chemokine receptors and the gastrointestinal system

Miyazaki¹,

Takabe²,

Yeudall³

2013

WJG

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Core tip: The chemokine network makes an attractive target for therapeutic intervention in many tumor types, including those of the gastrointestinal tract. However, we need to define more selective and specific targets, to minimize systemic side effects during treatment. INTRODUCTION Cancer development and progression in the gastrointestinal tractCancer is a disease in which normal cells acquire genetic and epigenetic abnormalities [1,2] , leading to disorientation of conventional processes for the maintenance of normal cell physiology. These aberrant genetic and epigenetic modifications to the normal cell induce abnormal cell motility, proliferation, and survival, eventually enabling these cells to invade into adjacent tissues and even to migrate to regional or distant organs where they may grow continuously as metastatic lesions [3] . For many cancer patients, metastasis is generally the major cause of disease-related death [4,5] . Therefore, it is indispensable to elucidate the basic molecular mechanisms of tumor development to identify effective therapeutic targets, which can possibly reduce the side-effects of treatment, and define useful molecular markers for early detection and prediction of disease course. Especially, the newly emerged concept of personalized medicine may require in-depth assessment of potential therapeutic molecular target(s) in each individual case through analysis of sig- REVIEW Chemokines, chemokine receptors and the gastrointestinal system AbstractThe biological properties of tumor cells are known to be regulated by a multitude of cytokines and growth factors, which include epidermal growth factor receptor agonists and members of the transforming growth factor β family. Furthermore, the recent explosion of research in the field of chemokine function as mediators of tumor progression has led to the possibility that these small, immunomodulatory proteins also play key roles in carcinogenesis and may, therefore, be potential targets for novel therapeutic approaches. In this review, we will summarize recently reported findings in chemokine biology with a focus on the gastrointestinal tract.

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CXCR4/SDF-1 axis is involved in lymph node metastasis of gastric carcinoma

Abstract: The CXCR4/SDF-1 axis is involved in the lymph node metastasis of gastric cancer. CXCR4 is considered as a potential therapeutic target in the treatment of gastric cancer.

Cited by 65 publications

References 34 publications

Hypoxia induces CXCR4 expression and biological activity in gastric cancer cells through activation of hypoxia-inducible factor-1α

Hypoxia induces CXCR4 expression and biological activity in gastric cancer cells through activation of hypoxia-inducible factor-1α

Gene therapy of gastric cancer using LIGHT-secreting human umbilical cord blood-derived mesenchymal stem cells

Chemokines, chemokine receptors and the gastrointestinal system

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