脑透明质酸结合蛋白抑制肿瘤生长。

Gao Feng, Cao Man-lin, Wang Lei

Department of Clinical Laboratory, Sixth People's Hospital, Medical School, Shanghai Jiaotong University, 200233, China.

Chin Med J (Engl). 2004 Jul;117(7):1072-8.

BACKGROUND

Great efforts have been made to search for the angiogenic inhibitors in avascular tissues. Several proteins isolated from cartilage have been proved to have anti-angiogenic or anti-tumour effects. Because cartilage contains a great amount of hyaluronic acid (HA) oligosaccharides and abundant HA binding proteins (HABP), therefore, we speculated that HABP might be one of the factors regulating vascularization in cartilage or anti-angiogenesis in tumours. The purpose of this research was to evaluate the effects of hyaluronan binding protein on inhibiting tumour growth both in vivo and vitro.

METHODS

A unique protein termed human brain hyaluronan (HA) binding protein (b-HABP) was cloned from human brain cDNA library. MDA-435 human breast cancer cell line was chosen as a transfectant. The in vitro underlying mechanisms were investigated by determining the possibilities of MDA-435/b-HABP colony formation on soft agar, the effects of the transfectant on the proliferation of endothelial cells and the expression levels of caspase 3 and FasL from MDA-435/b-HABP. The in vivo study included tumour growth on the chorioallantoic membrane (CAM) of chicken embryos and nude mice.

RESULTS

Colony formation assay revealed that the colonies formed by MDA-435/b-HABP were greatly reduced compared to mock transfectants. The conditioned media from MDA-435/b-HABP inhibited the growth of endothelial cells in culture. Caspase 3 and FasL expressions were induced by MDA-435/b-HABP. The size of tumours of MDA-435/b-HABP in both CAM and nude mice was much smaller than that of MDA-435 alone.

CONCLUSIONS

Human brain hyaluronan binding protein (b-HABP) may represent a new kind of naturally existing anti-tumour substance. This brain-derived glycoprotein may block tumour growth by inducing apoptosis of cancer cells or by decreasing angiogenesis in tumour tissue via inhibiting proliferation of endothelial cells.

背景

人们已付出巨大努力在无血管组织中寻找血管生成抑制剂。从软骨中分离出的几种蛋白质已被证明具有抗血管生成或抗肿瘤作用。由于软骨含有大量透明质酸（HA）寡糖和丰富的HA结合蛋白（HABP），因此，我们推测HABP可能是调节软骨血管生成或肿瘤抗血管生成的因素之一。本研究的目的是评估透明质酸结合蛋白在体内和体外对抑制肿瘤生长的作用。

方法

从人脑cDNA文库中克隆出一种独特的蛋白质，即人脑透明质酸（HA）结合蛋白（b-HABP）。选择MDA-435人乳腺癌细胞系作为转染细胞。通过测定MDA-435/b-HABP在软琼脂上形成集落的可能性、转染细胞对内皮细胞增殖的影响以及MDA-435/b-HABP中caspase 3和FasL的表达水平，研究其体外潜在机制。体内研究包括鸡胚绒毛尿囊膜（CAM）和裸鼠上的肿瘤生长情况。

结果

集落形成试验显示，与 mock转染细胞相比，MDA-435/b-HABP形成的集落大大减少。MDA-435/b-HABP的条件培养基抑制培养的内皮细胞生长。MDA-435/b-HABP诱导caspase 3和FasL表达。MDA-435/b-HABP在CAM和裸鼠中的肿瘤大小均比单独的MDA-435小得多。