Liby Karen, Neltner Bonnie, Mohamet Lisa, Burd Craig, Ben-Jonathan Nira
Department of Cell Biology, University of Cincinnati Medical School, Ohio 45267-0521, USA.
Cancer Biol Ther. 2003 Jan-Feb;2(1):48-52. doi: 10.4161/cbt.179.
Tumors must induce the formation of new blood vessels in order to grow and metastasize. Endostatin, a cleaved product of collagen XVIII, inhibits endothelial cell proliferation and suppresses tumor growth and metastases. Several recent reports have questioned the efficacy of endostatin as a tumor suppressor in experimental animals. Our objective was to determine whether endostatin expression in breast cancer cells inhibits neovascularization and tumor growth in nude mice. MDA-MB-435 cells were transfected with an endostatin expression vector while control cells were transfected with an empty vector. Endostatin expression and secretion were confirmed by RT-PCR and a dot blot assay. No differences were observed in the growth rates of the endostatin-expressing and control clones in vitro. When injected into male and female nude mice, tumors from the control clones increased in size 10-15 fold over 8-10 weeks. In contrast, the endostatin clones formed small tumors which did not increase in size after the first 3 weeks. The endostatinderived tumors had a significantly higher apoptotic index (5.6%) compared to controls (2.0%) and showed a marked reduction in vascularization. In conclusion, expression of endostatin in MDA-MB-435 breast cancer cells effectively suppressed breast tumor growth by inhibiting angiogenesis and increasing apoptosis.
肿瘤若要生长和转移，必须诱导新血管的形成。内皮抑素是胶原蛋白 XVIII 的裂解产物，可抑制内皮细胞增殖，并抑制肿瘤生长和转移。最近的几份报告对内皮抑素在实验动物中作为肿瘤抑制因子的功效提出了质疑。我们的目的是确定乳腺癌细胞中内皮抑素的表达是否能抑制裸鼠的新血管形成和肿瘤生长。用内皮抑素表达载体转染 MDA-MB-435 细胞，而对照细胞用空载体转染。通过 RT-PCR 和斑点印迹法确认内皮抑素的表达和分泌。在体外，表达内皮抑素的克隆和对照克隆的生长速率未观察到差异。当注射到雄性和雌性裸鼠体内时，对照克隆的肿瘤在 8 - 10 周内大小增加了 10 - 15 倍。相比之下，内皮抑素克隆形成的小肿瘤在最初 3 周后大小没有增加。与对照（2.0%）相比，内皮抑素衍生的肿瘤具有显著更高的凋亡指数（5.6%），并且血管化明显减少。总之，MDA-MB-435 乳腺癌细胞中内皮抑素的表达通过抑制血管生成和增加凋亡有效地抑制了乳腺肿瘤的生长。
