Division of Hematology-Oncology, University of Cincinnati Cancer Institute, Cincinnati, Ohio, USA.
Prostate. 2012 Nov;72(15):1669-77. doi: 10.1002/pros.22520. Epub 2012 Apr 2.
Matrigels, solubilized basement membrane preparations, are often used to support tumor development in animal models. However, tumors formed by a mixture of tumor cells and Matrigel may vary significantly. The purpose of this study was to compare tumor development and growth of LNCaP human prostate cancer cells mixed with Matrigel or in gelatin sponges.
LNCaP cells were mixed with Matrigel or absorbed into VETSPON, a gelatin sponge, and inoculated into the subcutis of nude mice. Tumor incidence and growth rate were determined. Gene expression and cell growth and survival in tumor lesions were evaluated by immunohistochemistry (IHC), immunoblotting, and RT-PCR.
All mice (12/12) inoculated with LNCaP cells in VETSPON produced tumors, compared to 70% (19/27) of mice injected with the cells with Matrigel. Tumor volume also varied less with VETSPON implants. No significant differences were observed in gene expression, cell growth, apoptosis, and microvessel density in tumors established from the two types of implants. However, in samples collected on days 1 and 4, more cells in Matrigel implants than those in VETSPON implants were stained positive for cleaved-caspase 3 and -PARP1. Expression of VEGF-A, HIF-1α, and Bcl-2 was elevated in the early VETSPON implants.
These data indicate that VETSPON promotes tumor cell survival at the early stage of implantation and suggest that the gelatin sponge is superior to Matrigel in supporting development and progression of human prostate cancer in nude mice. This model should be useful for preclinical studies in nude mice using LNCaP cells.
Matrigels 是一种可溶基底膜制剂,常用于支持动物模型中的肿瘤发展。然而,由肿瘤细胞和 Matrigels 混合物形成的肿瘤可能存在很大差异。本研究旨在比较 LNCaP 人前列腺癌细胞与 Matrigels 或明胶海绵混合后在体内的肿瘤发展和生长情况。
将 LNCaP 细胞与 Matrigels 混合或吸收到 VETSPON(一种明胶海绵)中,并接种到裸鼠的皮下。测定肿瘤发生率和生长速度。通过免疫组织化学(IHC)、免疫印迹和 RT-PCR 评估肿瘤病变中的基因表达以及细胞生长和存活情况。
所有接种 VETSPON 中 LNCaP 细胞的小鼠(12/12)均产生肿瘤,而接种 Matrigels 中细胞的小鼠(27/27)中只有 70%产生肿瘤。VETSPON 植入物的肿瘤体积变化也较小。两种植入物中建立的肿瘤在基因表达、细胞生长、凋亡和微血管密度方面没有观察到显著差异。然而,在第 1 天和第 4 天收集的样本中,Matrigels 植入物中的细胞比 VETSPON 植入物中的细胞有更多的 cleaved-caspase 3 和 -PARP1 染色阳性。早期 VETSPON 植入物中 VEGF-A、HIF-1α 和 Bcl-2 的表达升高。
这些数据表明 VETSPON 在植入早期促进肿瘤细胞存活,并表明明胶海绵在支持裸鼠中 LNCaP 细胞的发展和进展方面优于 Matrigels。该模型应可用于使用 LNCaP 细胞的裸鼠临床前研究。