Cellular changes in the tumor microenvironment of human esophageal squamous cell carcinomas

Abstract

The growth, invasiveness, and metastasis of human cancers are not only determined by the cancer cells but also by their microenvironment. The purpose of this study was to extend our previous studies and to examine the cellular changes in tumor microenvironment (stroma) of esophageal squamous cell carcinomas (ESCCs). The proliferative activity, cellular components, and angiogenesis status in different compartments (non-tumor stroma, tumor stroma, and tumor periphery stroma) of ESCCs were evaluated by immunohistochemistry. The results revealed a hyperproliferative rate labeled by Ki-67 in stromal cells in tumor area as compared with that in stromal cells in non-tumor area, which resulted in the increased densities of myofibroblasts (labeled by smooth muscle actin (SMA)-alpha), lymphocytes (labeled by CD3), macrophages (labeled by CD68), and the activation of angiogenesis characterized by increased microvessel density (MVD) and the increased expression of the proangiogenic factors (vascular endothelial growth factor and interleukin 8) in the tumor stroma. Further analysis showed that the changes of stromal cell density were more significant in the area of periphery tumor stroma than that of stroma between tumor nests. Most cellular changes were significantly associated with lymph node involvement. Double immunohistochemistries with PCNA/CD3, PCNA/CD68, and PCNA/SMA-alpha revealed that these cells present in the ESCC tumor stroma had a proliferative capacity. The cells present in the tumor microenvironment of ESCCs were greatly activated, suggesting that microenvironmental components may be involved in the cancer growth and progression.

Tumour–stroma crosstalk in the development of squamous cell carcinoma

“…Oesophageal SCC exhibit changes in stromal cell density shown to be increased in the peripheral tumour stroma when compared with stroma between tumour nests. The same study also showed that significantly higher SMA positive myofibroblasts which exhibited higher proliferative capacity correlated with tumour size (Liu, Li et al 2012). Studies on initiated, pre-malignant epithelial cells indicate that neoplastic growth is not necessarily stimulated when cultured with normal fibroblasts even under ideal conditions.…”

Immunohistochemical Analysis of Inflammatory Cells in Benign and Precancerous Lesions and Carcinoma of the Prostate

“…Several reports have indicated an important role for infiltrative monocyte chemotactic protein-1 (MCPs) in cancer development and stated that tumor-associated macrophage (TAM) infiltration was found to be closely correlated with poor outcomes in several types of human malignancies [4,5,6,7]. In lung cancer, pancreatic cancer, and glioma, CD204 + macrophages infiltrate around the tumor and contribute to progression.…”

Manganese-Enhanced MRI Reveals Early-Phase Radiation-Induced Cell Alterations In Vivo

“…In our study, the number of Ki-67-positive cells (potential marker of tumor growth activity; refs. 44,45) and the MEMRI signal were decreased at 24 hours after irradiation (Fig. 5F).…”