Role of cancer-associated stromal fibroblasts in metastatic colon cancer to the liver and their expression profiles

Hidewaki Nakagawa, Sandya Liyanarachchi, Ramana V. Davuluri, Herbert Auer, Edward W. Martin, Albert De La Chapelle, Wendy L. Frankel*

*Corresponding author for this work

Research output: Contribution to journalArticle

166 Scopus citations

Abstract

The cancer microenvironment and interaction between cancer and stromal cells play critical roles in tumor development and progression. The molecular features of cancer stroma are less well understood than those of cancer cells. Cancer-associated stromal fibroblasts are the predominant component of stroma associated with colon cancer and its functions remain unclear. Fibroblast cell cultures were established from metastatic colon cancer in liver, liver away from the metastatic lesions, and skin from three patients with metastatic colorectal cancer. We generated expression profiles of cancer-associated fibroblasts using oligochip arrays and compared them to those of uninvolved fibroblasts. The conditioned media from the cancer-associated fibroblast cultures enhanced proliferation of colon cancer cell line HCT116 to a greater extent than cultures from uninvolved fibroblasts. In microarray expression analysis, cancer-associated fibroblasts clustered tightly into one group and skin fibroblasts into another. Approximately 170 of 22000 genes were upregulated in cancer-associated fibroblasts (fold change > 2, P < 0.05) as compared to skin fibroblasts, including many genes encoding cell adhesion molecules, growth factors, and COX2. By immunohistochemistry in-vivo, we confirmed COX2 and TGFB2 expression in cancer-associated fibroblasts in metastatic colon cancer. The distinct molecular expression profiles of cancer-associated fibroblasts in colon cancer metastasis support the notion that these fibroblasts form a favorable microenvironment for cancer cells.

Original languageEnglish (US)
Pages (from-to)7366-7377
Number of pages12
JournalOncogene
Volume23
Issue number44
DOIs
StatePublished - Sep 23 2004

Keywords

  • COX2
  • Cancer microenvironment
  • Cancer-associated stroma
  • Colon cancer

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Nakagawa, H., Liyanarachchi, S., Davuluri, R. V., Auer, H., Martin, E. W., De La Chapelle, A., & Frankel, W. L. (2004). Role of cancer-associated stromal fibroblasts in metastatic colon cancer to the liver and their expression profiles. Oncogene, 23(44), 7366-7377. https://doi.org/10.1038/sj.onc.1208013