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Stroma-Directed Molecular Targeted Therapy in Gastric Cancer
Department of Gastroenterology and Metabolism, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Kasumi Minami-ku, Hiroshima 734-8551, Japan
* Author to whom correspondence should be addressed.
Received: 11 October 2011; in revised form: 22 November 2011 / Accepted: 30 November 2011 / Published: 8 December 2011
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.
Keywords: gastric cancer; stroma; platelet-derived growth factor receptor (PDGFR); carcinoma-associated fibroblast (CAF)
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Kitadai, Y.; Kodama, M.; Shinagawa, K. Stroma-Directed Molecular Targeted Therapy in Gastric Cancer. Cancers 2011, 3, 4245-4257.
Kitadai Y, Kodama M, Shinagawa K. Stroma-Directed Molecular Targeted Therapy in Gastric Cancer. Cancers. 2011; 3(4):4245-4257.
Kitadai, Yasuhiko; Kodama, Michiyo; Shinagawa, Kei. 2011. "Stroma-Directed Molecular Targeted Therapy in Gastric Cancer." Cancers 3, no. 4: 4245-4257.