Abstract
Recent studies in molecular and cellular biology have shown that tumor growth and metastasis are not determined by cancer cells alone, but also by a variety of stromal cells. Tumor stroma contains abundant extracellular matrix and several types of cells, including carcinoma-associated fibroblasts (CAFs), endothelial cells, pericytes and inflammatory cells including macrophages. In gastric cancer tissues, tumor cells express platelet-derived growth factor (PDGF)-B. Stromal cells, including CAFs, pericytes and lymphatic endothelial cells, express PDGF receptor (PDGFR)-β. Administration of PDGFR tyrosine kinase inhibitor significantly decreases stromal reaction, lymphatic vessel area and pericyte coverage of tumor microvessels. Administration of PDGFR tyrosine kinase inhibitor in combination with cytotoxic chemotherapeutic drug(s) impairs the progressive growth and metastasis of gastric cancer. Activated stroma might serve as a novel therapeutic target in cases of gastric cancer.
Highlights
Gastric cancer is the world’s fourth most common malignancy and the second leading cause of cancer death
Experiments have shown that carcinoma-associated fibroblasts (CAFs) can affect sensitivity of pancreatic carcinoma cells to chemo- or radio-therapy; the tumor cells become less sensitive to chemotherapy when co-cultured with CAFs or grown in fibroblast-conditioned medium [26]
CAFs have been implicated in important aspects of solid tumor biology including tumor growth, angiogenesis and metastasis, the precise origins of CAFs are not clear [27]
Summary
Gastric cancer is the world’s fourth most common malignancy and the second leading cause of cancer death. H. pylori inoculation into the stomach of Mongolian gerbils was shown to be associated with the occurrence of chronic gastritis, intestinal metaplasia and adenocarcinoma [3,4]. Chronic mucosal inflammation induced by H. pylori infection is thought to contribute significantly to the pathogenesis of atrophic gastritis, intestinal metaplasia, dysplasia, and gastric cancers. Recent studies have shown that tumor growth and metastasis are determined by cancer cells themselves, and by a variety of stromal cells. The stroma constitutes a large part of most solid tumors, and tumor-stromal cell interaction contributes functionally to tumor growth and metastasis [7,8]. We discuss the importance of tumor-stromal cell interaction in the growth and metastasis of human gastric cancer and the possibility of stroma-oriented therapy to reduce the risk of cancer metastasis, focusing mainly on CAFs
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