title: Fibroblast phenotypes in different lung diseases.
abstract: BACKGROUND
  The "seed and soil" hypothesis emphasizes the importance of interactions between tumor cells and their microenvironment. CAFs (Cancer associated fibroblasts) are important components of the tumor microenvironment. They were widely involved in cancer cells growth and metastasis. Fibroblasts may also play a role in inflammatory disease. The phenotype conversion of fibroblasts in lung diseases has not been investigated previously. We hypothesized that fibroblasts phenotypes may vary among different types of lung disease.
  
  
  METHODS
  The study included six types of lung tissues, ranging from normal lung to lung adenocarcinoma with lymphatic metastasis. Para-carcinoma tissues which were 2-cm-away from the tumor focus were also included in the analysis. The expression of target proteins including alpha-SMA (smooth muscle actin), FAP (fibroblast activation protein), vimentin, E-cadherin, and CK-19 (cytokeratin-19) were examined by immunohistochemistry. TGF-beta(transforming growth factor) and Twist were detected simultaneously in all samples.
  
  
  RESULTS
  A progressive increase in the levels of alpha-SMA, vimentin and CK-19 was observed in correlation to the degree of malignancy from normal lung tissue to lung adenocarcinoma with lymphatic metastasis, whereas E-cadherin expression showed the opposite trend. TGF-beta and Twist were detected in cancer tissues and inflammatory pseudotumors. None of the proteins were detected in para-carcinoma tissues.
  
  
  CONCLUSIONS
  Fibroblast phenotypes varied according to the type and degree of lung malignancy and fibroblasts phenotypic conversion occurs as a gradual process with specific spatiotemporal characteristics. Similar fibroblast phenotypes in inflammatory diseases and cancer tissues suggested a correlation between inflammation and cancer and implied a common mechanism underlying the formation of fibroblasts in inflammatory diseases and lung cancer.
authors.forename: Heng
authors.initials: H
authors.lastname: Du
authors.forename: Dali
authors.initials: D
authors.lastname: Chen
authors.forename: Yubin
authors.initials: Y
authors.lastname: Zhou
authors.forename: Zhaojie
authors.initials: Z
authors.lastname: Han
authors.forename: Guowei
authors.initials: G
authors.lastname: Che
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000293:Adolescent; D000328:Adult; D000368:Aged; D015820:Cadherins / Q000378:metabolism; D010450:Endopeptidases; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D018093:Gelatinases / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000166:cytology / Q000378:metabolism; D008171:Lung Diseases / Q000378:metabolism / Q000473:pathology*; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism; D010641:Phenotype; D012697:Serine Endopeptidases / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D051879:Twist-Related Protein 1 / Q000378:metabolism; D055815:Young Adult; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D015820:Cadherins; D010450:Endopeptidases; D018093:Gelatinases; D008565:Membrane Proteins; D009687:Nuclear Proteins; D012697:Serine Endopeptidases; D016212:Transforming Growth Factor beta; D051879:Twist-Related Protein 1; D000099167:Fibroblast Activation Protein Alpha; C103173:TWIST1 protein, human