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Overexpression of Solute Carrier Family in Ambient Particulate Matter Exposure Fibroblasts Enhances Lung Cancer Progression
Author(s) -
Chang Yu-Chan,
Hsiao Michael
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.00331
Subject(s) - lung cancer , downregulation and upregulation , copd , in vivo , chemistry , carcinogenesis , cancer research , transcriptome , cancer cell , tumor microenvironment , cell culture , pathology , cancer , microbiology and biotechnology , biology , medicine , biochemistry , gene expression , genetics , gene
Ambient Particulate Matter (PM) is considered to be air pollution and is correlated with pulmonary disease, particularly chronic obstructive pulmonary disease (COPD) and cancer. PM contains small particles and liquid droplets which then cause local inflammation and further systemic diseases. Characterization of HPF after PM exposure in lung tumorigenesis. We established transcriptomics through PM exposing to human pulmonary primary fibroblasts (HPF) under time‐course conditions. Our results preformed that PM exposure in HPF cells has upregulated the expression levels of several solute carrier family (SLCs). Therefore, we hypothesized that HPF may pump out or accelerate the production of metabolites to build up a tumor microenvironment. We detected SLC6A6 (taurine transporter), SLC7A11 (cysteine/glutamate transporter), SLC16A6/A7 (monocarboxylate transporter), SLC37A4 (glucose‐6‐phosphate exchanger) and SLC35F1 (lung squamous cell cancer related protein) were increased in HPF models by qPCR analysis. In addition, we demonstrated that the relevant metabolites indeed increased the production of HPF cell culture supernatants. Moreover, we determined that these transporters have been upregulated by immunohistochemical staining in the lung region of the intratracheal injection in vivo model. Furthermore, we processed an indirect co‐culture system between HPF and benign lung cancer cells. We then observed that lung cancer cells can enhance their migration/invasion ability under HPF‐PM exposure culture medium. We also track fluorescence‐based signals from nanobubble‐embbed metabolites in vitro and in vivo . Meanwhile, we recruited analogs of each metabolites or competitors to block with transporters. These data indicate that the phenotype can be reversed in the indirectly culture system. Combining all observations, we concluded that several metabolites may allow fibroblasts to acquire functions similar to cancer‐associated fibroblasts (CAFs). Cancer cells prevent nutrient deprivation by activating metabolic reprogramming of adjacent fibroblasts. These antagonists can serve as a novel strategy for neutralizing the tumor microenvironment of pulmonary diseases.