The CXCL12-CXCR4 Signaling Axis Plays a Key Role in Cancer Metastasis and is a Potential Target for Developing Novel Therapeutics against Metastatic Cancer

Yang, Ping; Hu, Yae; Zhou, Quansheng

doi:10.2174/0929867326666191113113110

Cited by 29 publications

(25 citation statements)

References 168 publications

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“…Several studies have demonstrated that the CXCR4/CXCL12 axis plays a crucial role in organ-specific metastasis formation [28][29][30]. CXCL12, a ligand for CXCR4, is abundantly produced by neighboring stromal cells and activation of CXCR4-expressing cancer cells by CXCL12 leads to enhanced chemotaxis, trans-endothelial migration, and invasion.…”

Section: Discussionmentioning

confidence: 99%

An Extract of Olive Mill Wastewater Downregulates Growth, Adhesion and Invasion Pathways in Lung Cancer Cells: Involvement of CXCR4

et al. 2020

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Several diet-derived compounds have been reported to exert antioxidant, anti-proliferative and anti-angiogenic effects in numerous cancers and could be beneficial in cancer prevention. Olive oil production involves the generation of an aqueous phase defined as olive mill wastewater (OMWW), a polluting effluent rich in soluble polyphenols. Here, we assessed the cancer preventive properties exerted by a purified extract of OMWW (A009) for its activity on lung cancer cell lines. Hydroxytyrosol, the most abundant polyphenol present in our A009 extracts, was used as reference molecule in the assays performed. Extracts from OMWW from two different olive oil cultivars were used. We found that the A009 extracts limit lung cancer cell proliferation in a dose and time dependent manner. These effects were associated with the induction of apoptosis. A009 extracts were effective in inhibiting adhesion capabilities on a fibronectin layer accompanied with a reduction in their ability to generate invasive sprouts in a Matrigel layer. The production of chemokine CXCL12 and CXCR4 receptor were reduced by treatment with the extracts. Also, A009 interfered with the production of proangiogenic and pro-inflammatory VEGF, CXCL8, and CCL2 (as detected by FACS analysis) in the lung cell lines. A009 extracts were able to decrease STAT3 phosphorylation in lung cancer cells. Our results show that A009 extracts reduced activities related to tumor cell behavior in lung cancer cell lines, suggesting that they could have a potential cancer preventive role.

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Section: Discussionmentioning

confidence: 99%

An Extract of Olive Mill Wastewater Downregulates Growth, Adhesion and Invasion Pathways in Lung Cancer Cells: Involvement of CXCR4

et al. 2020

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“…This microenvironment is known as the pre‐metastatic niche. Indeed, CXCL12/CXCR4 signaling contributes to the development of the pre‐metastatic niche and disruption of CXCL12/CXCR4 signaling is effective in inhibiting metastasis 83,87‐89 …”

Section: Endothelial Cellsmentioning

confidence: 99%

Tumor microenvironment in gastric cancers

2020

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The tumor microenvironment favors the growth and expansion of cancer cells. Many cell types are involved in the tumor microenvironment such as inflammatory cells, fibroblasts, nerves, and vascular endothelial cells. These stromal cells contribute to tumor growth by releasing various molecules to either directly activate the growth signaling in cancer cells or remodel surrounding areas. This review introduces recent advances in findings on the interactions within the tumor microenvironment such as in cancer‐associated fibroblasts (CAFs), immune cells, and endothelial cells, in particular those established in mouse gastric cancer models. In mice, myofibroblasts in the gastric stroma secrete R‐spondin and support normal gastric stem cells. Most CAFs promote tumor growth in a paracrine manner, but CAF population appears to be heterogeneous in terms of their function and origin, and include both tumor‐promoting and tumor‐restraining populations. Among immune cell populations, tumor‐associated macrophages, including M1 and M2 macrophages, and myeloid‐derived suppressor cells (MDSCs), are reported to directly or indirectly promote gastric tumorigenesis by secreting soluble factors or modulating immune responses. Endothelial cells or blood vessels not only fuel tumors with nutrients, but also interact with cancer stem cells and immune cells by secreting chemokines or cytokines, and act as a cancer niche. Understanding these interactions within the tumor microenvironment would contribute to unraveling new therapeutic targets.

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“…The CXCL12‐CXCR4 signaling regulates organogenesis, hematopoiesis, and angiogenesis during gestational development and lymphocyte development 100‐103 as well as the typical chemokine functions for the recruitment of immune cells such as dendritic cells and lymphocytes 104,105 . The CXCL12‐CXCR4 axis is well known to promote cancer development and metastasis by enhancing angiogenesis, cell migration, and EMT 106‐108 . Thus, CXCL14 inhibition of CXCL12 binding to CXCR4 may be a pertinent mechanism of CXCL14‐mediated tumor suppression.…”

Section: Cxcl14 Candidate Receptorsmentioning

confidence: 99%

The multifarious roles of the chemokine CXCL14 in cancer progression and immune responses

Westrich

Vermeer

Colbert

et al. 2020

Molecular Carcinogenesis

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The chemokine CXCL14 is a highly conserved, homeostatic chemokine that is constitutively expressed in skin epithelia. Responsible for immune cell recruitment and maturation, as well as impacting epithelial cell motility, CXCL14 contributes to the establishment of immune surveillance within normal epithelial layers. Furthermore, CXCL14 is critical to upregulating major histocompatibility complex class I expression on tumor cells. Given these important roles, CXCL14 is often dysregulated in several types of carcinomas including cervical, colorectal, endometrial, and head and neck cancers. Its disruption has been shown to limit critical antitumor immune regulation and is correlated to poor patient prognosis.However, other studies have found that in certain cancers, namely pancreatic and some breast cancers, overexpression of stromal CXCL14 correlates with poor patient survival due to increased invasiveness. Contributing to the ambiguity CXCL14 plays in cancer is that the native CXCL14 receptor remains uncharacterized, although several candidate receptors have been proposed.Despite the complexity of CXCL14 functions, it remains clear that this chemokine is a key regulatory factor in cancer and represents a potential target for future cancer immunotherapies. K E Y W O R D Santitumor immunity, chemokine, CXCL14, HPV, immunotherapy

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The CXCL12-CXCR4 Signaling Axis Plays a Key Role in Cancer Metastasis and is a Potential Target for Developing Novel Therapeutics against Metastatic Cancer

Cited by 29 publications

References 168 publications

An Extract of Olive Mill Wastewater Downregulates Growth, Adhesion and Invasion Pathways in Lung Cancer Cells: Involvement of CXCR4

An Extract of Olive Mill Wastewater Downregulates Growth, Adhesion and Invasion Pathways in Lung Cancer Cells: Involvement of CXCR4

Tumor microenvironment in gastric cancers

The multifarious roles of the chemokine CXCL14 in cancer progression and immune responses

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