Department of Gastroenterology and Metabolism, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Kasumi Minami-ku, Hiroshima 734-8551, Japan.
Cancers (Basel). 2011 Dec 8;3(4):4245-57. doi: 10.3390/cancers3044245.
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.
最近的分子和细胞生物学研究表明，肿瘤的生长和转移不仅取决于癌细胞，还取决于各种基质细胞。肿瘤基质含有丰富的细胞外基质和几种类型的细胞，包括癌相关成纤维细胞（CAFs）、内皮细胞、周细胞和炎症细胞，如巨噬细胞。在胃癌组织中，肿瘤细胞表达血小板衍生生长因子（PDGF）-B。基质细胞，包括 CAFs、周细胞和淋巴管内皮细胞，表达 PDGF 受体（PDGFR）-β。给予 PDGFR 酪氨酸激酶抑制剂可显著减少基质反应、淋巴管面积和肿瘤微血管周细胞的覆盖。联合使用 PDGFR 酪氨酸激酶抑制剂和细胞毒性化疗药物可损害胃癌的进行性生长和转移。激活的基质可能成为胃癌的一个新的治疗靶点。
