Analysis of differential gene expression patterns in colon cancer and cancer stroma using microdissected tissues

Gastroenterology. 2005 Feb;128(2):480-6. doi: 10.1053/j.gastro.2004.11.010.

Abstract

Background and aims: The surrounding cancer stroma is increasingly recognized as playing an important role in cancer proliferation, invasion, and metastasis. Here, we analyzed patterns of gene expression in colon cancer cells, surrounding stroma, and normal mucosa and normal stroma using laser capture microdissection.

Methods: Tissues were fixed from 11 patients undergoing colorectal resection for cancer, and laser capture microdissection was performed. Samples (4 per patient) were extracted for RNA, which was then used for focused gene arrays. In addition, protein expression of selected genes was determined by Western blot or immunohistochemistry.

Results: We showed differential expression patterns in cancer cells and surrounding stroma compared with their normal counterparts. Genes contributing to angiogenesis, cell cycle regulation, and proliferation were significantly increased in cancer cells compared with the adjacent normal mucosa. Genes contributing to angiogenesis, cancer invasion, and metastasis were significantly increased in surrounding cancer stromal cells compared with normal stroma.

Conclusions: Delineating the differential patterns of gene expression between colon cancers and the surrounding reactive stroma will better determine the role of the stromal components in the progression of colon cancers and may lead to chemopreventive therapy targeted specifically to the stroma.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Adenocarcinoma / surgery
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / pathology*
  • Colonic Neoplasms / surgery
  • Gene Expression Regulation
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Intestinal Mucosa / pathology
  • Oligonucleotide Array Sequence Analysis
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / isolation & purification
  • Reference Values
  • Stromal Cells / pathology

Substances

  • RNA, Neoplasm