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The chemokine CXCL13 in lung cancers associated with environmental polycyclic aromatic hydrocarbons pollution.

Wang GZ, Cheng X, Zhou B, Wen ZS, Huang YC, Chen HB, Li GF, Huang ZL, Zhou YC, Feng L, Wei MM, Qu LW, Cao Y, Zhou GB - Elife (2015)

Bottom Line: Here, we screened for abnormal inflammatory factors in non-small cell lung cancers (NSCLCs) from Xuanwei and control regions (CR) where smoky coal was not used, and found that a chemokine CXCL13 was overexpressed in 63/70 (90%) of Xuanwei NSCLCs and 44/71 (62%) of smoker and 27/60 (45%) of non-smoker CR patients.CXCL13 overexpression was associated with the region Xuanwei and cigarette smoke.Deficiency in Cxcl13 or its receptor, Cxcr5, significantly attenuated BaP-induced lung cancer in mice, demonstrating CXCL13's critical role in PAH-induced lung carcinogenesis.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

ABSTRACT
More than 90% of lung cancers are caused by cigarette smoke and air pollution, with polycyclic aromatic hydrocarbons (PAHs) as key carcinogens. In Xuanwei City of Yunnan Province, the lung cancer incidence is among the highest in China, attributed to smoky coal combustion-generated PAH pollution. Here, we screened for abnormal inflammatory factors in non-small cell lung cancers (NSCLCs) from Xuanwei and control regions (CR) where smoky coal was not used, and found that a chemokine CXCL13 was overexpressed in 63/70 (90%) of Xuanwei NSCLCs and 44/71 (62%) of smoker and 27/60 (45%) of non-smoker CR patients. CXCL13 overexpression was associated with the region Xuanwei and cigarette smoke. The key carcinogen benzo(a)pyrene (BaP) induced CXCL13 production in lung epithelial cells and in mice prior to development of detectable lung cancer. Deficiency in Cxcl13 or its receptor, Cxcr5, significantly attenuated BaP-induced lung cancer in mice, demonstrating CXCL13's critical role in PAH-induced lung carcinogenesis.

No MeSH data available.


Related in: MedlinePlus

Activation of β-catenin and epithelial mesenchymal transition (EMT) in benzo(a)pyrene (BaP)-induced lung cancer.(A) The expression of indicated genes in lung tissues from A/J mice treated with BaP and/or dexamethasone (DEX) was detected by real-time PCR. (B) Western blot analyses of lysates of lung tissues from A/J mice treated with BaP and/or DEX. (C) Western blot analyses of cytoplasmic and nucleic protein fractions of lung tissues from A/J mice treated with BaP and/or DEX, using indicated antibodies. (D) Western blot analysis of lysates of lung tissues from NOD/SCID mice injected with indicated cells. (E) Western blot analyses of cytoplasmic and nucleic protein fractions in lung tissues from NOD/SCID mice injected with indicated cells. (F) Western blot analyses of lysates of lung tissues from Cxcr5 mutant mice treated with BaP. (G) IHC assays for the expression of β–catenin in Cxcr5 mutant mice upon BaP. (H) Immunofluorescence analyses of β-catenin in A549 cells transfected with control vector (V) or SPP1, or treated with THP-1 supernatant (Mϕs.) or supernatant of THP-1 cells co-incubated with CXCL13 (M13s.). (I) Western blot analyses of cytoplasmic and nucleic protein fractions of A549 cells transfected with control vector (V) or SPP1, or treated with Mϕs. or M13s. (J) Real-time PCR assays of indicated genes in A549 cells transfected with control vector or SPP1, or treated with Mϕs. or M13s. (K) Western blot analyses of lysates of A549 cells transfected with control vector (V) or SPP1, or treated with Mϕs. or M13s, using indicated antibodies.DOI:http://dx.doi.org/10.7554/eLife.09419.018
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fig6s1: Activation of β-catenin and epithelial mesenchymal transition (EMT) in benzo(a)pyrene (BaP)-induced lung cancer.(A) The expression of indicated genes in lung tissues from A/J mice treated with BaP and/or dexamethasone (DEX) was detected by real-time PCR. (B) Western blot analyses of lysates of lung tissues from A/J mice treated with BaP and/or DEX. (C) Western blot analyses of cytoplasmic and nucleic protein fractions of lung tissues from A/J mice treated with BaP and/or DEX, using indicated antibodies. (D) Western blot analysis of lysates of lung tissues from NOD/SCID mice injected with indicated cells. (E) Western blot analyses of cytoplasmic and nucleic protein fractions in lung tissues from NOD/SCID mice injected with indicated cells. (F) Western blot analyses of lysates of lung tissues from Cxcr5 mutant mice treated with BaP. (G) IHC assays for the expression of β–catenin in Cxcr5 mutant mice upon BaP. (H) Immunofluorescence analyses of β-catenin in A549 cells transfected with control vector (V) or SPP1, or treated with THP-1 supernatant (Mϕs.) or supernatant of THP-1 cells co-incubated with CXCL13 (M13s.). (I) Western blot analyses of cytoplasmic and nucleic protein fractions of A549 cells transfected with control vector (V) or SPP1, or treated with Mϕs. or M13s. (J) Real-time PCR assays of indicated genes in A549 cells transfected with control vector or SPP1, or treated with Mϕs. or M13s. (K) Western blot analyses of lysates of A549 cells transfected with control vector (V) or SPP1, or treated with Mϕs. or M13s, using indicated antibodies.DOI:http://dx.doi.org/10.7554/eLife.09419.018

Mentions: At least two tumors were found in left and/or right lungs of each BaP-treated mouse (Figure 2—figure supplement 1B), and CXCL13 induced cancer cell migration and metastasis (Figure 5F–I, Figure 6E). We tested the epithelial mesenchymal transition (EMT) phenotypes that are associated with cancer progression and metastasis (Kalluri and Weinberg, 2009) in tumor samples from the BaP-treated A/J mice, and found that the expression of E-Cadherin was down-regulated, while N-Cadherin, Vimentin, Slug and Snail were up-regulated (Figure 6—figure supplement 1A). At protein level, E-Cadherin was down-regulated, while N-Cadherin and Vimentin were up-regulated in the tumors (Figure 6—figure supplement 1B). β-catenin transport to the nucleus is critical for cells to enter into an EMT and acquire an invasive phenotype (Kim, 2002). We showed that the nuclear β-catenin levels were increased in the tumor samples from A/J mice (Figure 6—figure supplement 1C). In the tumor samples from NOD/SCID mice injected with A549-Luc-CXCL13 cells (Figure 6—figure supplement 1D,E) and BaP-treated Cxcr5+/+ mice (Figure 6—figure supplement 1F,G), the expression of E-Cadherin was low, while the N-Cadherin and nuclear β-catenin were high.


The chemokine CXCL13 in lung cancers associated with environmental polycyclic aromatic hydrocarbons pollution.

Wang GZ, Cheng X, Zhou B, Wen ZS, Huang YC, Chen HB, Li GF, Huang ZL, Zhou YC, Feng L, Wei MM, Qu LW, Cao Y, Zhou GB - Elife (2015)

Activation of β-catenin and epithelial mesenchymal transition (EMT) in benzo(a)pyrene (BaP)-induced lung cancer.(A) The expression of indicated genes in lung tissues from A/J mice treated with BaP and/or dexamethasone (DEX) was detected by real-time PCR. (B) Western blot analyses of lysates of lung tissues from A/J mice treated with BaP and/or DEX. (C) Western blot analyses of cytoplasmic and nucleic protein fractions of lung tissues from A/J mice treated with BaP and/or DEX, using indicated antibodies. (D) Western blot analysis of lysates of lung tissues from NOD/SCID mice injected with indicated cells. (E) Western blot analyses of cytoplasmic and nucleic protein fractions in lung tissues from NOD/SCID mice injected with indicated cells. (F) Western blot analyses of lysates of lung tissues from Cxcr5 mutant mice treated with BaP. (G) IHC assays for the expression of β–catenin in Cxcr5 mutant mice upon BaP. (H) Immunofluorescence analyses of β-catenin in A549 cells transfected with control vector (V) or SPP1, or treated with THP-1 supernatant (Mϕs.) or supernatant of THP-1 cells co-incubated with CXCL13 (M13s.). (I) Western blot analyses of cytoplasmic and nucleic protein fractions of A549 cells transfected with control vector (V) or SPP1, or treated with Mϕs. or M13s. (J) Real-time PCR assays of indicated genes in A549 cells transfected with control vector or SPP1, or treated with Mϕs. or M13s. (K) Western blot analyses of lysates of A549 cells transfected with control vector (V) or SPP1, or treated with Mϕs. or M13s, using indicated antibodies.DOI:http://dx.doi.org/10.7554/eLife.09419.018
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4764582&req=5

fig6s1: Activation of β-catenin and epithelial mesenchymal transition (EMT) in benzo(a)pyrene (BaP)-induced lung cancer.(A) The expression of indicated genes in lung tissues from A/J mice treated with BaP and/or dexamethasone (DEX) was detected by real-time PCR. (B) Western blot analyses of lysates of lung tissues from A/J mice treated with BaP and/or DEX. (C) Western blot analyses of cytoplasmic and nucleic protein fractions of lung tissues from A/J mice treated with BaP and/or DEX, using indicated antibodies. (D) Western blot analysis of lysates of lung tissues from NOD/SCID mice injected with indicated cells. (E) Western blot analyses of cytoplasmic and nucleic protein fractions in lung tissues from NOD/SCID mice injected with indicated cells. (F) Western blot analyses of lysates of lung tissues from Cxcr5 mutant mice treated with BaP. (G) IHC assays for the expression of β–catenin in Cxcr5 mutant mice upon BaP. (H) Immunofluorescence analyses of β-catenin in A549 cells transfected with control vector (V) or SPP1, or treated with THP-1 supernatant (Mϕs.) or supernatant of THP-1 cells co-incubated with CXCL13 (M13s.). (I) Western blot analyses of cytoplasmic and nucleic protein fractions of A549 cells transfected with control vector (V) or SPP1, or treated with Mϕs. or M13s. (J) Real-time PCR assays of indicated genes in A549 cells transfected with control vector or SPP1, or treated with Mϕs. or M13s. (K) Western blot analyses of lysates of A549 cells transfected with control vector (V) or SPP1, or treated with Mϕs. or M13s, using indicated antibodies.DOI:http://dx.doi.org/10.7554/eLife.09419.018
Mentions: At least two tumors were found in left and/or right lungs of each BaP-treated mouse (Figure 2—figure supplement 1B), and CXCL13 induced cancer cell migration and metastasis (Figure 5F–I, Figure 6E). We tested the epithelial mesenchymal transition (EMT) phenotypes that are associated with cancer progression and metastasis (Kalluri and Weinberg, 2009) in tumor samples from the BaP-treated A/J mice, and found that the expression of E-Cadherin was down-regulated, while N-Cadherin, Vimentin, Slug and Snail were up-regulated (Figure 6—figure supplement 1A). At protein level, E-Cadherin was down-regulated, while N-Cadherin and Vimentin were up-regulated in the tumors (Figure 6—figure supplement 1B). β-catenin transport to the nucleus is critical for cells to enter into an EMT and acquire an invasive phenotype (Kim, 2002). We showed that the nuclear β-catenin levels were increased in the tumor samples from A/J mice (Figure 6—figure supplement 1C). In the tumor samples from NOD/SCID mice injected with A549-Luc-CXCL13 cells (Figure 6—figure supplement 1D,E) and BaP-treated Cxcr5+/+ mice (Figure 6—figure supplement 1F,G), the expression of E-Cadherin was low, while the N-Cadherin and nuclear β-catenin were high.

Bottom Line: Here, we screened for abnormal inflammatory factors in non-small cell lung cancers (NSCLCs) from Xuanwei and control regions (CR) where smoky coal was not used, and found that a chemokine CXCL13 was overexpressed in 63/70 (90%) of Xuanwei NSCLCs and 44/71 (62%) of smoker and 27/60 (45%) of non-smoker CR patients.CXCL13 overexpression was associated with the region Xuanwei and cigarette smoke.Deficiency in Cxcl13 or its receptor, Cxcr5, significantly attenuated BaP-induced lung cancer in mice, demonstrating CXCL13's critical role in PAH-induced lung carcinogenesis.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

ABSTRACT
More than 90% of lung cancers are caused by cigarette smoke and air pollution, with polycyclic aromatic hydrocarbons (PAHs) as key carcinogens. In Xuanwei City of Yunnan Province, the lung cancer incidence is among the highest in China, attributed to smoky coal combustion-generated PAH pollution. Here, we screened for abnormal inflammatory factors in non-small cell lung cancers (NSCLCs) from Xuanwei and control regions (CR) where smoky coal was not used, and found that a chemokine CXCL13 was overexpressed in 63/70 (90%) of Xuanwei NSCLCs and 44/71 (62%) of smoker and 27/60 (45%) of non-smoker CR patients. CXCL13 overexpression was associated with the region Xuanwei and cigarette smoke. The key carcinogen benzo(a)pyrene (BaP) induced CXCL13 production in lung epithelial cells and in mice prior to development of detectable lung cancer. Deficiency in Cxcl13 or its receptor, Cxcr5, significantly attenuated BaP-induced lung cancer in mice, demonstrating CXCL13's critical role in PAH-induced lung carcinogenesis.

No MeSH data available.


Related in: MedlinePlus