SDF-1/CXCR7 axis regulates the proliferation, invasion, adhesion, and angiogenesis of gastric cancer cells

Ma, Demin; Luo, Dian-Xi; Zhang, Jie

doi:10.1186/s12957-016-1009-z

Cited by 25 publications

(23 citation statements)

References 31 publications

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“…The decreased expression of CXCR4 and the concomitant increase in CXCR7 in H295R cells, in response to the increased level of SDF-1 measured in ASC conditioned medium, suggests a preferential activation of the CXCL12/CXCR7-related signaling in this co-culture system. A similar CXCR7 over-expression has been described in a variety of cancers, with particular implication for cancer initiation, progression and metastasis [47][48][49][50][51][52][53], mainly mediated via ERK activation [54,55]. In addition, CXCR7 seems essential for the process of trans-endothelial migration, that is a pivotal step for supporting tumor cell entrance in the bloodstream and metastasis [56].…”

Section: Discussionmentioning

confidence: 61%

The Adipose Stem Cell as a Novel Metabolic Actor in Adrenocortical Carcinoma Progression: Evidence from an In Vitro Tumor Microenvironment Crosstalk Model

Armignacco

Cantini

Poli

et al. 2019

Cancers

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Metabolic interplay between the tumor microenvironment and cancer cells is a potential target for novel anti-cancer approaches. Among stromal components, adipocytes and adipose precursors have been shown to actively participate in tumor progression in several solid malignancies. In adrenocortical carcinoma (ACC), a rare endocrine neoplasia with a poor prognosis, cancer cells often infiltrate the fat mass surrounding the adrenal organ, enabling possible crosstalk with the adipose cells. Here, by using an in vitro co-culture system, we show that the interaction between adipose-derived stem cells (ASCs) and the adrenocortical cancer cell line H295R leads to metabolic and functional reprogramming of both cell types: cancer cells limit differentiation and increase proliferation of ASCs, which in turn support tumor growth and invasion. This effect associates with a shift from the paracrine cancer-promoting IGF2 axis towards an ASC-associated leptin axis, along with a shift in the SDF-1 axis towards CXCR7 expression in H295R cells. In conclusion, our findings suggest that adipose precursors, as pivotal components of the ACC microenvironment, promote cancer cell reprogramming and invasion, opening new perspectives for the development of more effective therapeutic approaches.

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Section: Discussionmentioning

confidence: 61%

The Adipose Stem Cell as a Novel Metabolic Actor in Adrenocortical Carcinoma Progression: Evidence from an In Vitro Tumor Microenvironment Crosstalk Model

Armignacco

Cantini

Poli

et al. 2019

Cancers

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“…Regarding the biological functions of CXCL12 and CXCR7 in cells, existing reports have focused on cell proliferation 47 , invasion 48 and migration 49 . To date, the role of CXCR7 in regulating angiogenesis in HUVECs has remained unclear.…”

Section: Discussionmentioning

confidence: 99%

CXCL12 enhances angiogenesis through CXCR7 activation in human umbilical vein endothelial cells

Zhang

Qiu

Zhang

et al. 2017

Sci Rep

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Angiogenesis is the process by which new vessels form from existing vascular networks. Human umbilical vein endothelial cells (HUVECs) may contribute to the study of vascular repair and angiogenesis. The chemokine CXCL12 regulates multiple cell functions, including angiogenesis, mainly through its receptor CXCR4. In contrast to CXCL12/CXCR4, few studies have described roles for CXCR7 in vascular biology, and the downstream mechanism of CXCR7 in angiogenesis remains unclear. The results of the present study showed that CXCL12 dose-dependently enhanced angiogenesis in chorioallantoic membranes (CAMs) and HUVECs. The specific activation of CXCR7 with TC14012 (a CXCR7 agonist) resulted in the significant induction of tube formation in HUVECs and in vivo. Further evidence suggested that CXCL12 induced directional polarization and migration in the HUVECs, which is necessary for tube formation. Moreover, CXCR7 translocalization was observed during the polarization of HUVECs in stripe assays. Finally, treatment with TC14012 also significantly increased PI3K/Akt phosphorylation, and tube formation was blocked by treating HUVECs with an Akt inhibitor. Overall, this study indicated that CXCL12-stimulated CXCR7 acts as a functional receptor to activate Akt for angiogenesis in HUVECs and that CXCR7 may be a potential target molecule for endothelial regeneration and repair after vascular injury.

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“…CXCR7 is usually upregulated in GC tissues with a positivity rate of 63–84.62% by IHC, which correlates with deep invasion, LN metastasis, advanced stages, and bad outcome of patients . Also, CXCR7 is highly expressed in the majority of tumor‐associated vessels and related with tumor neovascularization via regulating the secretion of proangiogenic factors such as interleukin‐8 and VEGF . CXCR7 overexpression may affect disease progression by stimulating proliferation, invasion, migration, adhesion, and angiogenesis of GC through β ‐arrestin‐dependent downstream signalings, including Akt, ERK1/2, p38 MAPK, JAK2/STAT3, and stress‐activated protein kinase (SAPK) pathways .…”

Section: Cross‐talks Of Cxcl12/cxcr4 Axis With Other Chemokines and Cmentioning

confidence: 99%

“…Also, CXCR7 is highly expressed in the majority of tumor‐associated vessels and related with tumor neovascularization via regulating the secretion of proangiogenic factors such as interleukin‐8 and VEGF . CXCR7 overexpression may affect disease progression by stimulating proliferation, invasion, migration, adhesion, and angiogenesis of GC through β ‐arrestin‐dependent downstream signalings, including Akt, ERK1/2, p38 MAPK, JAK2/STAT3, and stress‐activated protein kinase (SAPK) pathways . CXCL11, also known as interferon‐inducible T‐cell α chemoattractant (I‐TAC), induces chemoattraction and activation of T lymphocytes through CXCR3 that is preferentially expressed on both polarized type 1 helper T (Th1) and cytotoxic T lymphocytes .…”

Section: Cross‐talks Of Cxcl12/cxcr4 Axis With Other Chemokines and Cmentioning

confidence: 99%

Inhibition of CXCL12/CXCR4 axis as a potential targeted therapy of advanced gastric carcinoma

et al. 2017

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The whole outcome for patients with gastric carcinoma (GC) is very poor because most of them remain metastatic disease during survival even at diagnosis or after surgery. Despite many improvements in multiple strategies of chemotherapy, immunotherapy, and targeted therapy, exploration of novel alternative therapeutic targets is still warranted. Chemokine receptor 4 (CXCR4) and its chemokine ligand 12 (CXCL12) have been identified with significantly elevated levels in various malignancies including GC, which correlates with the survival, proliferation, angiogenesis, and metastasis of tumor cells. Increasing experimental evidence suggests an implication of inhibition of CXCL12/CXCR4 axis as a promising targeted therapy, although there are rare trials focused on the therapeutic efficacy of CXCR4 inhibitors in GC until recently. Therefore, it is reasonable to infer that specific antagonists or antibodies targeting CXCL12/CXCR4 axis alone or combined with chemotherapy will be effective and worthy of further translational studies as a potential treatment strategy in advanced GC.

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SDF-1/CXCR7 axis regulates the proliferation, invasion, adhesion, and angiogenesis of gastric cancer cells

Cited by 25 publications

References 31 publications

The Adipose Stem Cell as a Novel Metabolic Actor in Adrenocortical Carcinoma Progression: Evidence from an In Vitro Tumor Microenvironment Crosstalk Model

The Adipose Stem Cell as a Novel Metabolic Actor in Adrenocortical Carcinoma Progression: Evidence from an In Vitro Tumor Microenvironment Crosstalk Model

CXCL12 enhances angiogenesis through CXCR7 activation in human umbilical vein endothelial cells

Inhibition of CXCL12/CXCR4 axis as a potential targeted therapy of advanced gastric carcinoma

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