Melnyk O, Shuman M A, Kim K J
Cancer Research Institute, University of California, San Francisco 94143, USA.
Cancer Res. 1996 Feb 15;56(4):921-4.
Tumor growth is dependent on new blood vessel formation. Inhibition of vascular endothelial growth factor (VEGF), an endothelial cell mitogen and angiogenic factor secreted by a variety of tumors and tumor cell lines, is sufficient to inhibit primary tumor growth. In the present study, we examined the effect of inhibiting VEGF on tumor cell micrometastasis. A transfectant of A431 (a human epidermoid carcinoma cell line) expressing chloramphenicol acetyltransferase (CAT) was injected s.c. into severe combined immunodeficiency (scid) mice, which were then sacrificed after 6 weeks. The presence of A431 metastases at distant sites was demonstrated by detection of CAT activity in whole-organ lysates. Treatment of animals with VEGF-neutralizing antibodies not only inhibited primary tumor growth but also suppressed metastases, as determined by CAT activity in organ lysates. In experiments to determine the mechanism by which anti-VEGF antibody inhibited metastasis, control animals were sacrificed when their tumors had reached the same size as tumors in VEGF antibody-treated animals. Metastases were uniformly present in these control animals. These findings show that inhibition of VEGF alone is sufficient to prevent tumor growth and dissemination in vivo. The inhibitory effect on metastases appears to be distinct from that on primary tumor growth.
肿瘤生长依赖于新血管的形成。血管内皮生长因子（VEGF）是一种由多种肿瘤和肿瘤细胞系分泌的内皮细胞促有丝分裂剂和血管生成因子，抑制VEGF足以抑制原发性肿瘤生长。在本研究中，我们检测了抑制VEGF对肿瘤细胞微转移的影响。将表达氯霉素乙酰转移酶（CAT）的A431（一种人表皮样癌细胞系）转染子皮下注射到严重联合免疫缺陷（scid）小鼠体内，6周后处死小鼠。通过检测全器官裂解物中的CAT活性来证明远处部位存在A431转移灶。用VEGF中和抗体处理动物，不仅抑制了原发性肿瘤生长，还抑制了转移，这通过器官裂解物中的CAT活性来确定。在确定抗VEGF抗体抑制转移的机制的实验中，当对照动物的肿瘤大小与VEGF抗体处理动物的肿瘤大小相同时，将其处死。这些对照动物中均有转移灶。这些发现表明，单独抑制VEGF足以在体内预防肿瘤生长和扩散。对转移的抑制作用似乎与对原发性肿瘤生长的抑制作用不同。
