Human Adipose-Derived Mesenchymal Stem Cell-Secreted CXCL1 and CXCL8 Facilitate Breast Tumor Growth By Promoting Angiogenesis

Chang

et al. 2018

IJMS

Crosstalk of a tumor with its microenvironment is a critical factor contributing to cancer development. This study investigates the soluble factors released by tumor-associated dendritic cells (TADCs) responsible for increasing cancer stem cell (CSC) properties, cell mobility, and epithelial-to-mesenchymal transition (EMT). Dendritic cells (DCs) of colon cancer patients were collected for phenotype and CXCL1 expression by flow cytometry and Luminex assays. The transcriptome of CXCL1-treated cancer cells was established by next generation sequencing. Inflammatory chemokine CXCL1, present in large amounts in DCs isolated from colon cancer patients, and SW620-conditioned TADCs, enhance CSC characteristics in cancer, supported by enhanced anchorage-independent growth, CD133 expression and aldehyde dehydrogenase activity. Additionally, CXCL1 increases the metastatic ability of a cancer by enhancing cell migration, matrix metalloproteinase-7 expression and EMT. The enhanced CXCL1 expression in DCs is also noted in mice transplanted with colon cancer cells. Transcriptome analysis of CXCL1-treated SW620 cells indicates that CXCL1 increases potential oncogene expression in colon cancer, including PTHLH, TYRP1, FOXO1, TCF4 and ZNF880. Concurrently, CXCL1 displays a specific microRNA (miR) upregulated by the prototypical colon cancer onco-miR miR-105. Analysis of publicly available data reveals CXCL1-driven oncogenes and miR-105 have a negative prognostic impact on the outcome of colon cancer. This study indicates a new mechanism by which the colon cancer milieu exploits DC plasticity to support cancer progression.

Section: Discussionmentioning

confidence: 99%

Interaction between Tumor-Associated Dendritic Cells and Colon Cancer Cells Contributes to Tumor Progression via CXCL1

Hsu

Chang

et al. 2018

IJMS

“…CXCL1 promotes and exacerbates growth and progression of many tumors [40]. By activating CXCR2, CXCL1 is associated with cancer cell growth and proliferation, tumor angiogenesis and metastasis [41,42]. In tumor therapies, CXCL1 is also responsible for resistance of the cancer cells to several chemotherapeutic drugs [43].…”

Section: Discussionmentioning

confidence: 99%

Associations of CXCL1 gene 5’UTR variations with ovarian cancer

Guo

et al. 2020

J Ovarian Res

Background: There are about 2.4 hundred thousand new cases and 1.5 hundred thousand deaths of ovarian cancer (OC) annually in the world. Chronic inflammation is a risk factor for OC. C-X-C motif chemokine ligand 1 (CXCL1) defects may facilitate inflammation and transactivate EGFR in ovarian cancer, but the precise haplotypes associated with the potential diseases remained largely unknown. In this work, we characterized CXCL1 gene variations to elucidate their possible associations with OC.Methods: We analyzed the CXCL1 gene for 300 OC patients with 400 healthy participants as controls. The statistical analyses and Hardy-Weinberg equilibrium tests of the patients and control populations were conducted using the SPSS software (version 19.0) and Plink (version 1.9).Results: The variants rs11547681, rs201090116, rs199791199, rs181868085, rs4074 and rs1814092 within or near the CXCL1 gene were characterized. The genetic heterozygosity of rs11547681 and rs4074 was very high. Statistical analysis showed that the variant rs11547681 in the gene was closely associated with the risk of OC in the Chinese Han population, although this variant was not associated with FIGO stages or pathological grades of the patients. Conclusions: Rs11547681 in CXCL1 gene was associated with the risk of OC in the Chinese Han population.

“…CXCL1 promotes and exacerbates growth and progression of many tumors [40]. By activating CXCR2, CXCL1 is associated with cancer cell growth and proliferation, tumor angiogenesis and metastasis [41,42]. In tumor therapies, CXCL1 is also responsible for several chemotherapeutic drugs resistance [43].…”

Section: Discussionmentioning

confidence: 99%

Associations of CXCL1 gene 5’UTR variations with ovarian cancer

Guo

et al. 2020

Preprint

Background: There are about 2.4 hundred thousand new cases and 1.5 hundred thousand deaths of ovarian cancer (OC) annually in the world. Chronic inflammation is a risk factor for OC. C-X-C motif chemokine ligand 1 (CXCL1) defects may facilitate inflammation and transactivate EGFR in ovarian cancer, but the precise haplotypes associated with the potential diseases remained largely unknown. In this work, we characterized CXCL1 gene variations to elucidate their possible associations with OC. Methods: We analyzed the CXCL1 gene for 300 OC patients with 400 healthy participants as controls. The statistical analyses and Hardy-Weinberg equilibrium tests of the patients and control populations were conducted using the SPSS software (version 19.0) and Plink (version 1.9). Results: The variants rs11547681, rs201090116, rs199791199, rs181868085, rs4074 and rs1814092 within or near the CXCL1 gene were characterized. The genetic heterozygosity of rs11547681 and rs4074 was very high. Statistical analysis showed that the variant rs11547681 in the gene was closely associated with the risk of OC in the Chinese Han population, although this variant was not associated with FIGO stages or pathological grades of the patients. Conclusions: Rs11547681 in CXCL1 gene was associated with the risk of OC in the Chinese Han population.