Smooth muscle actin-expressing stromal fibroblasts in head and neck squamous cell carcinoma: increased expression of galectin-1 and induction of poor prognosis factors

Int J Cancer. 2012 Dec 1;131(11):2499-508. doi: 10.1002/ijc.27550. Epub 2012 Apr 9.

Abstract

Tumor stroma is an active part influencing the biological properties of malignancies via molecular cross-talk. Cancer-associated fibroblasts play a significant role in this interaction. These cells frequently express smooth muscle actin and can be classified as myofibroblasts. The adhesion/growth-regulatory lectin galectin-1 is an effector for their generation. In our study, we set the presence of smooth muscle actin-positive cancer-associated fibroblasts in relation to this endogenous lectin and an in vivo competitor (galectin-3). In squamous cell carcinomas of head and neck, upregulation of galectin-1 presence was highly significantly correlated to presence of smooth muscle actin-positive cancer-associated fibroblasts in the tumor (p = 4 × 10(-8)). To pinpoint further correlations on the molecular level, we applied microarray analyses to the transcription profiles of the corresponding tumors. Significant correlations of several transcripts were detected with the protein level of galectin-1 in the cancer-associated fibroblasts. These activated genes (MAP3K2, TRIM23, PTPLAD1, FUSIP1, SLC25A40 and SPIN1) are related to known squamous-cell-carcinoma poor-prognosis factors, NF-κB upregulation and splicing downregulation. These results provide new insights into the significance of presence of myofibroblasts in squamous cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / biosynthesis*
  • Actins / genetics
  • Actins / metabolism
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology*
  • Down-Regulation
  • Female
  • Galectin 1 / biosynthesis*
  • Galectin 1 / genetics
  • Galectin 1 / metabolism
  • Galectin 3 / genetics
  • Galectin 3 / metabolism
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / metabolism*
  • Head and Neck Neoplasms / pathology*
  • Humans
  • Male
  • Muscle, Smooth / metabolism
  • Muscle, Smooth / pathology
  • Myofibroblasts / metabolism
  • Myofibroblasts / pathology
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Prognosis
  • RNA Splicing
  • Stromal Cells / metabolism
  • Stromal Cells / pathology
  • Transcription, Genetic
  • Up-Regulation

Substances

  • Actins
  • Galectin 1
  • Galectin 3
  • NF-kappa B