Collagen XVII expression correlates with the invasion and metastasis of colorectal cancer

Hum Pathol. 2015 Mar;46(3):434-42. doi: 10.1016/j.humpath.2014.11.020. Epub 2014 Dec 17.

Abstract

Collagen XVII has a well-established role as an adhesion molecule and a cell surface receptor located in the type I hemidesmosome of stratified epithelia. Its ectodomain is constitutively shed from the cell surface and suggested to regulate the adhesion, migration, and signaling of cutaneous epithelial cells. Collagen XVII was not previously thought to be expressed by colon epithelial cells. Immunohistochemical analysis of tissue microarray samples of 141 cases of colorectal carcinoma showed that collagen XVII is expressed in normal human colonic mucosa and colorectal carcinoma. In colorectal carcinoma, increased collagen XVII expression was significantly associated with higher TNM stage. It also correlated with infiltrative growth pattern and tumor budding as well as lymph node and distant metastasis. Increased collagen XVII expression was associated with decreased disease-free and cancer-specific survival. Immunofluorescence staining of collagen XVII and its well-known binding partner laminin γ2 chain demonstrated a partial colocalization in normal and tumor tissue. In vitro, the overexpression of murine collagen XVII promoted the invasion of CaCo-2 colon carcinoma cells through Matrigel (BD Biosciences; Bedford, MA). To conclude, this study reports for the first time the expression of collagen XVII in colon epithelium and the association of increased collagen XVII immunoexpression with poor outcome in colorectal carcinoma.

Keywords: Adhesion; BP180; Basement membrane; Collagen XVII; Colorectal cancer; Hemidesmosome; Invasion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Autoantigens / analysis*
  • Basement Membrane / chemistry
  • Basement Membrane / pathology
  • Biomarkers, Tumor / analysis*
  • Caco-2 Cells / chemistry
  • Caco-2 Cells / pathology
  • Collagen Type XVII
  • Colorectal Neoplasms / chemistry*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / therapy
  • Disease-Free Survival
  • Female
  • Fluorescent Antibody Technique
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Intestinal Mucosa / chemistry*
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / pathology*
  • Neoplasm Staging
  • Neoplasms, Squamous Cell / chemistry*
  • Neoplasms, Squamous Cell / mortality
  • Neoplasms, Squamous Cell / pathology
  • Neoplasms, Squamous Cell / secondary*
  • Neoplasms, Squamous Cell / therapy
  • Non-Fibrillar Collagens / analysis*
  • ROC Curve
  • Survival Analysis
  • Treatment Outcome

Substances

  • Autoantigens
  • Biomarkers, Tumor
  • Non-Fibrillar Collagens