Efficient inhibition of intra-peritoneal tumor growth and dissemination of human ovarian carcinoma cells in nude mice by anti-L1-cell adhesion molecule monoclonal antibody treatment
Efficient inhibition of intra-peritoneal tumor growth and dissemination of human ovarian carcinoma cells in nude mice by anti-L1-cell adhesion molecule monoclonal antibody treatment
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DOI：
10.1158/0008-5472.can-05-1818
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发表时间：
2006-01-15
期刊：
影响因子：
11.2
通讯作者：
Krüger, A
中科院分区：
文献类型：
--
作者：
Arlt, MJE;Novak-Hofer, I;Krüger, A
L1细胞粘附分子在体外参与控制几种肿瘤细胞类型的增殖、迁移和侵袭。最近，L1过表达被发现与卵巢癌的肿瘤进展相关，卵巢癌是妇科恶性疾病中癌症相关死亡的最常见原因之一。为了评估L1作为卵巢癌治疗的潜在靶点，我们在体外研究了抗L1单克隆抗体（chCE7和L1- 11a）对L1阳性人SKOV3ip卵巢癌细胞增殖和迁移的影响，以及L1- 11a对裸鼠i.p. SKOV3ip肿瘤生长的治疗效果。在体外实验中，两种抗l1抗体均能有效抑制SKOV3ip细胞以及其他表达l1的肿瘤细胞系（肾癌、神经母细胞瘤和结肠癌）的增殖。在两种细胞系中，L1- 11a与一种二抗的超交联是显著抑制增殖所必需的，这表明L1的交联是抗增殖作用所必需的。l1阴性前列腺癌细胞不受抗体处理的影响。每两周用L1-11A治疗卵巢癌小鼠，导致肿瘤负荷（高达-63.5%）和腹水形成（高达-75%）的剂量依赖性和显著减少。这种效果与肿瘤内的增殖减少有关。以l1为导向的抗体抑制人卵巢癌细胞的腹膜生长和播散，为开发一种针对主要妇科恶性疾病的新疗法提供了重要的原理证明。
The L1 cell adhesion molecule is implicated in the control of proliferation, migration, and invasion of several tumor cell types in vitro. Recently, L1 overexpression was found to correlate with tumor progression of ovarian carcinoma, one of the most common causes of cancer-related deaths in gynecologic malignant diseases. To evaluate L1 as a potential target for ovarian cancer therapy, we investigated the effects of anti-L1 monoclonal antibodies (chCE7 and L1-11A) on proliferation and migration of L1-positive human SKOV3ip ovarian carcinoma cells in vitro and the therapeutic efficacy of L1-11A against i.p. SKOV3ip tumor growth in nude mice. In vitro, both anti-L1 antibodies efficiently inhibited the proliferation of SKOV3ip cells as well as other L1-expressing tumor cell lines (renal carcinoma, neuroblastoma, and colon carcinoma). On two cell lines, hyper-cross-linking of L1-11A with a secondary antibody was necessary for significant inhibition of proliferation, indicating that cross-linking of L1 is required for the antiproliferative effect. L1-negative prostate carcinoma cells were not influenced by antibody treatment. Biweekly treatment of ovarian carcinoma-bearing mice with L1-11A led to a dose-dependent and significant reduction of tumor burden (up to -63.5%) and ascites formation (up to -75%). This effect was associated with reduced proliferation within the tumors. L1-directed antibody-based inhibition of peritoneal growth and dissemination of human ovarian carcinoma cells represents important proof-of-principle for the development of a new therapy against one of the leading gynecologic malignant diseases.