Clinical significance and biological role of cancer-derived Type I collagen in lung and esophageal cancers

Abstract

Background: Extracellular matrix (ECM) is remodeled during carcinogenesis. An abundant constituent of ECM is collagen. Type I collagen is secreted by fibroblasts, is important for tumor growth and epithelial-mesenchymal transition, and may also be secreted by cancer cells. However, the role and function of cancer-derived Type I collagen in the tumor microenvironment remains unclear. Methods: We used immunohistochemistry and Western blot to detect Type I collagen expression in non-small cell lung cancer (NSCLC) and esophageal squamous cell carcinoma (ESCC) cell lines, respectively. We assessed the migration and adhesion capability of these cells in vivo by inhibiting Type I collagen in tumors. Relevant data were extracted from a large cohort study of The Cancer Genome Atlas to analyze messenger RNA levels. Protein expression of Type I collagen was further determined in tumor tissues of patients using tissue microarray. Results: Cancer cell lines secreted Type I collagen. The molecular weight of cancer-derived Type I collagen was different from that secreted by cancer-associated fibroblasts and normal fibroblasts. Expression levels of COL1A1 and COL1A2 (subtypes of Type I collagen) messenger RNA in NSCLC and ESCC tumors were higher than in normal tissues, but were not associated with tumor node metastasis stages. Low expression of Type I collagen was significantly associated with poor overall survival and cancer cell differentiation. Conclusion: NSCLC and ESCC cells could produce Type I collagen endogenously, revealing the potential functions of Type I collagen in cancer development. Cancer-derived Type I collagen was associated with overall survival and cancer cell differentiation. © 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd