ABSTRACT
Epidermal growth factor receptor (EGFR) signaling is an important pathway that is not only involved in the determination of cellular development, but also has significant roles in tumor development and progression. The study aims to examine the expression of EGFR signaling pathway-related proteins (EGFR, c-Fos, and c-erb-B2) in esophageal squamous cell carcinoma and to investigate their relationships with clinical significance. Sixty esophageal squamous carcinoma specimens obtained by fiber esophagoscope were subjected to two-step immunohistochemistry to test the expression of EGFR, c-Fos, and c-erb-B2. EGFR expression was observed in 73.3% of tumors (44/60); positive EGFR expression was significantly correlated with tumor-node-metastasis (TNM) staging, lymph node metastasis, and distant metastasis (P < 0.05). c-Fos expression was found in 85% (51/60) of tumors, and its expression was significantly related to tumor depth and TNM staging (P < 0.05). c-erb-B2 expression was 75% (45/60) in esophageal squamous cell carcinoma (ESCC) specimens, and positive-erb-B2 expression had a significant association with the depth of tumor invasion (P < 0.05). c-Fos expression was significantly and positively correlated with c-erb-B2 (P < 0.05). Overexpression of EGFR, c-Fos, and c-erb-B2 was associated with tumor progression and development. EGFR and c-Fos expression can predict the tumor stage. c-Fos and c-erb-B2 expression can be used to determine the depth of tumor invasion and can also act as a combined prognostic indicator in ESCC.
Subject(s)
Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , ErbB Receptors/metabolism , Esophageal Neoplasms/metabolism , Esophageal Neoplasms/pathology , Signal Transduction , Adult , Aged , Carcinoma, Squamous Cell/genetics , ErbB Receptors/genetics , Esophageal Neoplasms/genetics , Esophageal Squamous Cell Carcinoma , Female , Gene Expression , Humans , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Proto-Oncogene Proteins c-fos/genetics , Proto-Oncogene Proteins c-fos/metabolism , Receptor, ErbB-2/genetics , Receptor, ErbB-2/metabolismABSTRACT
OBJECTIVE: To separate/enrich tumor stem-like cells from the human esophageal carcinoma cell line OE-19 by using serum-free suspension culture and to identify their biological characteristics and radiation resistance. METHODS: OE-19 cells were cultivated using adherent and suspension culture methods. The tumor stem-like phenotype of CD44 expression was detected using flow cytometry. We examined growth characteristics, cloning capacity in soft agar, and radiation resistance of 2 groups of cells. RESULTS: Suspended cells in serum-free medium formed spheres that were enriched for CD44 expression. CD44 was expressed in 62.5% of suspended cells, but only in 11.7% of adherent cells. The suspended cells had greater capacity for proliferation and colony formation in soft agar than the adherent cells. When the suspended and adherent cells were irradiated at 5 Gy, 10 Gy, or 15 Gy, the proportion of CD44+ suspended cells strongly and weakly positive for CD44 was 77.8%, 66.5%, 57.5%; and 21.7%, 31.6%, 41.4%, respectively. In contrast, the proportion of CD44+ adherent cells strongly positive for CD44 was 18.9%, 14.%, and 9.95%, respectively. When the irradiation dose was increased to 30 Gy, the survival of the suspended and adherent cells was significantly reduced, and viable CD44+ cells were not detected. CONCLUSION: Suspended cell spheres generated from OE-19 esophageal carcinoma cells in serum-free stem medium are enriched in tumor stem-like cells. CD44 may be a marker for these cells.
