Tumor-Derived CXCL1 Promotes Lung Cancer Growth via Recruitment of Tumor-Associated Neutrophils

Yuan, Ming; Zhu, Hongyan; Xu, Junfang; Zheng, Yuanyuan; Cao, Xuetao; Liu, Qiuyan

doi:10.1155/2016/6530410

Cited by 77 publications

(74 citation statements)

References 49 publications

(49 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent evidence demonstrated that CXCL1 enhanced tumor growth via recruitment of neutrophils into the tumor microenvironment. For example, tumor cell-secreted CXCL1 promoted lung cancer growth via recruitment of neutrophils into tumor tissue in vivo (35). TNFα stimulates mesenchymal stromal cells to produce CXCR2 ligands that recruit CXCR2 + neutrophils into primary tumors in a mouse model of breast cancer (36).…”

Section: Discussionmentioning

confidence: 99%

CXCL1 Is Critical for Premetastatic Niche Formation and Metastasis in Colorectal Cancer

et al. 2017

View full text Add to dashboard Cite

Emerging evidence suggests that the primary tumor influences the development of supportive metastatic microenvironments, referred to as pre-metastatic niches, in certain distant organs before arrival of metastatic cells. However, the mechanisms underlying the contributions of the primary tumor to pre-metastatic niche formation are not fully understood. Here we demonstrate that colorectal carcinoma cells secrete VEGF-A, which stimulates tumor-associated macrophages to produce CXCL1 in the primary tumor. Elevation of CXCL1 in pre-metastatic liver tissue recruited CXCR2-positive myeloid-derived suppressor cells (MDSC) to form a pre-metastatic niche that ultimately promoted liver metastases. Importantly, pre-metastatic liver-infiltrating MDSC induced tumor cell survival without involvement of innate or adaptive immune responses. Our study provides the first evidence that primary malignant cell-secreted VEGF-A stimulates tumor-associated macrophages to produce CXCL1, which recruits CXCR2-positive MDSC to form a pre-metastatic niche to promote liver metastases. Our findings not only shed light on how the tumor microenvironment contributes to pre-metastatic niche formation at distant sites, but they also provide comprehensive insights into how MDSC are recruited to other organs where they contribute to metastatic spread of disease. Moreover, our work also provides a rational for development of CXCR2 antagonists to inhibit or prevent metastatic spread of disease.

show abstract

Section: Discussionmentioning

confidence: 99%

CXCL1 Is Critical for Premetastatic Niche Formation and Metastasis in Colorectal Cancer

et al. 2017

View full text Add to dashboard Cite

show abstract

“…TNFα directly endorses tumor progression and metastasis . Furthermore, CXCL1 has been reported to facilitate lung cancer cell growth due to the recruitment of MDSCs and tumor associated neutrophils . Importantly, all of these factors were also found to be upregulated in K‐ras G12D ‐mutated lung alveolar type II (K) cells compared to WT cells or in tumor harboring lungs from KP mice compared to non‐tumorous lungs from KP mice.…”

Section: Discussionmentioning

confidence: 99%

“…48 Furthermore, CXCL1 has been reported to facilitate lung cancer cell growth due to the recruitment of MDSCs and tumor associated neutrophils. 13,49 Importantly, all of these factors were also found to be upregulated in K-ras G12D -mutated lung alveolar type II (K) cells compared to WT cells or in tumor harboring lungs from KP mice compared to non-tumorous lungs from KP mice. In agreement with this data, low mRNA expression levels of lL6, Tnfα and IL8 (the human orthologue to murine Cxcl1) were also associated with a better prognosis in lung AC patients harboring K-RAS mutations.…”

Section: Discussionmentioning

confidence: 99%

JAK–STAT inhibition impairs K‐RAS‐driven lung adenocarcinoma progression

Mohrherr

Haber

Breitenecker

et al. 2019

Intl Journal of Cancer

View full text Add to dashboard Cite

Oncogenic K‐RAS has been difficult to target and currently there is no K‐RAS‐based targeted therapy available for patients suffering from K‐RAS‐driven lung adenocarcinoma (AC). Alternatively, targeting K‐RAS‐downstream effectors, K‐RAS‐cooperating signaling pathways or cancer hallmarks, such as tumor‐promoting inflammation, has been shown to be a promising therapeutic strategy. Since the JAK–STAT pathway is considered to be a central player in inflammation‐mediated tumorigenesis, we investigated here the implication of JAK–STAT signaling and the therapeutic potential of JAK1/2 inhibition in K‐RAS‐driven lung AC. Our data showed that JAK1 and JAK2 are activated in human lung AC and that increased activation of JAK–STAT signaling correlated with disease progression and K‐RAS activity in human lung AC. Accordingly, administration of the JAK1/2 selective tyrosine kinase inhibitor ruxolitinib reduced proliferation of tumor cells and effectively reduced tumor progression in immunodeficient and immunocompetent mouse models of K‐RAS‐driven lung AC. Notably, JAK1/2 inhibition led to the establishment of an antitumorigenic tumor microenvironment, characterized by decreased levels of tumor‐promoting chemokines and cytokines and reduced numbers of infiltrating myeloid derived suppressor cells, thereby impairing tumor growth. Taken together, we identified JAK1/2 inhibition as promising therapy for K‐RAS‐driven lung AC.

show abstract

“…The levels of CXCL1 are elevated in CRC and increased levels are associated with tumor size, advancing stage and patient survival 37,38 . It was reported that CXCL1 could promote tumor growth by inducing angiogenesis and recruiting neutrophils into the tumor associated microenvironment 39,40 . CXCL1, most abundant secreted chemokine by tumor-associated macrophages (TAMs) have been implicated in the promotion of breast cancer growth and metastasis via activating NF-κB/SOX4 signaling 41 .…”

Section: Discussionmentioning

confidence: 99%

Identification of Hub Gene TIMP1 and Relative ceRNAs Regulatory Network in Colorectal Cancer

Kong

Qin

et al. 2020

Preprint

View full text Add to dashboard Cite

Objectives This study aimed to discover the ceRNAs network in pathophysiological development of human colorectal cancer (CRC) and to screen biomarkers for target therapy and prognosis by using integrated bioinformatics analysis.Methods Data on gene expressions of mRNAs, circRNAs, and miRNAs and clinical information were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus database respectively. Differentially expressed mRNAs (DEGs) were identified by using DESeq2 package of R software. Functional enrichment analysis was conducted by ClusterProfiler package of R software. Protein-protein interaction (PPI) network was shown by STRING website. Survival analysis of hub genes was performed by survival package in R software. Interactions among hub gene, DEmiRNAs and DEcircRNAs were used to construct ceRNAs network.Results A total of 412 DEGs (including 82 upregulated and 330 downregulated) were screened out between 473 CRC and 41 normal samples. 260 DEcircRNAs (including 253 upregulated and 7 downregulated) were altered. A ceRNAs and PPI network was successfully constructed and TIMP1 associated with prognosis were employed.Conclusion The present study identifies a novel ceRNAs network, which imply that TIMP1 is a potential biomarker underlying the development of CRC, providing new insights for survival prediction and therapeutic target.

show abstract

Tumor-Derived CXCL1 Promotes Lung Cancer Growth via Recruitment of Tumor-Associated Neutrophils

Cited by 77 publications

References 49 publications

CXCL1 Is Critical for Premetastatic Niche Formation and Metastasis in Colorectal Cancer

CXCL1 Is Critical for Premetastatic Niche Formation and Metastasis in Colorectal Cancer

JAK–STAT inhibition impairs K‐RAS‐driven lung adenocarcinoma progression

Identification of Hub Gene TIMP1 and Relative ceRNAs Regulatory Network in Colorectal Cancer

Contact Info

Product

Resources

About