PLATELET-DERIVED GROWTH-FACTOR (PDGF) IN ONCOGENESIS - DEVELOPMENT OF A VASCULAR CONNECTIVE-TISSUE STROMA IN XENOTRANSPLANTED HUMAN-MELANOMA PRODUCING PDGF-BB
PLATELET-DERIVED GROWTH-FACTOR (PDGF) IN ONCOGENESIS - DEVELOPMENT OF A VASCULAR CONNECTIVE-TISSUE STROMA IN XENOTRANSPLANTED HUMAN-MELANOMA PRODUCING PDGF-BB
复制标题
DOI：
10.1073/pnas.90.2.393
复制
发表时间：
1993-01-15
影响因子：
11.1
通讯作者：
WESTERMARK, B
中科院分区：
文献类型：
--
作者：
FORSBERG, K;VALYINAGY, I;WESTERMARK, B
在巨细胞病毒启动子的转录控制下，用PDGF- b cDNA稳定转染了先前被证明缺乏PDGF表达的人类WM9黑色素瘤细胞。Northern blot分析显示pdgf - b转染的细胞中高表达了预期大小的mRNA。免疫沉淀法证实PDGF-BB的合成和分泌。此外，pdgf - b转染细胞的条件培养基含有成纤维细胞的有丝分裂活性。为了分析肿瘤在体内的生长情况，将每种类型的细胞皮下注射到BALB/c nu/nu小鼠中。用转染该载体的WM9细胞注射小鼠肿瘤后，肿瘤仅含有大面积坏死区域；仅见血管稀少，管腔狭窄。未见结缔组织。在pdgf - b转染的WM9细胞中，肿瘤巢被结缔组织间隔隔开。结缔组织间隔和肿瘤细胞巢内可见丰富的血管。这些肿瘤完全没有坏死。目前的结果表明，肿瘤来源的PDGF-BB是结缔组织间质形成的有效介质。响应PDGF-BB而产生的结缔组织框架可能对新形成的血管形成坚实的支持，从而促进肿瘤中功能性血管系统的形成。
Human WM9 melanoma cells, previously shown to be devoid of PDGF expression, were stably transfected with a PDGF-B cDNA under the transcriptional control of a cytomegalovirus promoter. Northern blot analysis revealed high expression of an mRNA of the expected size in the PDGF-B-transfected cells. Synthesis and secretion of PDGF-BB was confirmed by immunoprecipitation. Furthermore, conditioned medium from PDGF-B-transfected cells contained a mitogenic activity for fibroblasts. For analysis of tumor growth in vivo, cells of each type were injected subcutaneously into BALB/c nu/nu mice. Tumors from mice injected with WM9 cells transfected with the vector only contained large necrotic areas; only scant blood vessels with narrow lumina were observed. No connective tissue was present. In the tumors from PDGF-B-transfected WM9 cells, nests of tumor were divided by connective tissue septa. An abundance of blood vessels was observed in the connective tissue septa and within the tumor cell nests. There was a complete absence of necrosis in these tumors. The present results suggest that tumor-derived PDGF-BB is a potent mediator of connective tissue stroma formation. The connective tissue framework that is generated in response to PDGF-BB may form a solid support for newly formed blood vessels and, thereby, facilitate the formation of a functional vascular system in the tumor.