title: Tumor-associated macrophages: the double-edged sword in cancer progression.
abstract: OBJECTIVE
  Inflammation plays a critical role in cancer progression. In this study we investigate the pro-tumorigenic activities and gene expression profiles of lung cancer cells after interaction with macrophages.
  
  
  METHODS
  We measured intratumoral microvessel counts and macrophage density in 41 lung cancer tumor specimens and correlated these with the patients' clinical outcome. The interaction between macrophages and cancer cell lines was assessed using a transwell coculture system. The invasive potential was evaluated by in vitro invasion assay. The matrix-degrading activity was assayed by gelatin zymography. The microarray was applied to a large-scale analysis of the genes involved in the interaction, as well as to monitor the gene expression profiles of lung cancer cells responding to anti-inflammatory drugs in cocultures.
  
  
  RESULTS
  The macrophage density positively correlated with microvessel counts and negatively correlated with patient relapse-free survival (P < .05). After coculture with macrophages, lung cancer cell lines exhibited higher invasive potentials and matrix-degrading activities. We identified 50 genes by microarray that were upregulated more than two-fold in cancer cells after coculture. Northern blot analyses confirmed some gene expression such as interleukin-6, interleukin-8, and matrix metalloproteinase 9. The two-dimensional hierarchical clustering also demonstrated that the gene expression profiles of lung cancer cells responding to various anti-inflammatory drugs in cocultures are distinct.
  
  
  CONCLUSIONS
  The interaction of lung cancer cells and macrophages can promote the invasiveness and matrix-degrading activity of cancer cells. Our results also suggest that a great diversity of gene expression occurs in this interaction, which may assist us in understanding the process of cancer metastasis.
authors.affiliation: Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan, People's Republic of China.
authors.forename: Jeremy J W
authors.initials: JJ
authors.lastname: Chen
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Lin
authors.forename: Pei-Li
authors.initials: PL
authors.lastname: Yao
authors.forename: Ang
authors.initials: A
authors.lastname: Yuan
authors.forename: Hsang-Yu
authors.initials: HY
authors.lastname: Chen
authors.forename: Chia-Tung
authors.initials: CT
authors.lastname: Shun
authors.forename: Meng-Feng
authors.initials: MF
authors.lastname: Tsai
authors.forename: Chun-Houh
authors.initials: CH
authors.lastname: Chen
authors.forename: Pan-Chyr
authors.initials: PC
authors.lastname: Yang
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000235:genetics / Q000473:pathology; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000235:genetics / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000235:genetics / Q000473:pathology; D002452:Cell Count; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D018093:Gelatinases / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D008175:Lung Neoplasms / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000473:pathology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D008833:Microcirculation / Q000473:pathology; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D015854:Up-Regulation / Q000235:genetics
chemical_list: D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D016209:Interleukin-8; D018093:Gelatinases; D020780:Matrix Metalloproteinase 9