INTERFERENCE OF THE IGF SYSTEM AS A STRATEGY TO INHIBIT BREAST-CANCER GROWTH
INTERFERENCE OF THE IGF SYSTEM AS A STRATEGY TO INHIBIT BREAST-CANCER GROWTH
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DOI：
10.1007/bf01833338
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发表时间：
1992-01-01
影响因子：
3.8
通讯作者：
ARTEAGA, CL
中科院分区：
文献类型：
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作者：
ARTEAGA, CL
实验证据表明，人乳腺癌细胞可以调节IGF-I和IGF-II存在于肿瘤基质元素和/或内源性肿瘤细胞IGF-II的旁分泌或自分泌的方式。因此，受体信号传导途径的阻断可导致肿瘤生长减少。通过单克隆抗体（α-IR 3）阻断I型IGF受体已被用作证明IGF途径重要性的策略。虽然α-IR 3不能阻断乳腺癌细胞系的无血清生长，但它可以抑制大多数细胞系在血清存在下的锚定非依赖性生长。在体内，在肿瘤细胞接种时给予的α-IR 3可以抑制无胸腺小鼠中的MDA-MB-231肿瘤形成;然而，未观察到对已建立的肿瘤的抑制。此外，α-IR 3不能抑制MCF-7细胞系在体内的肿瘤形成。这些结果表明，I型IGF受体的阻断剂可以在体外和体内抑制一些乳腺癌细胞的生长。未来的抗生长因子策略包括抗IGF受体抗体与IGF中和方式的组合，生长因子受体（表皮生长因子受体和I型IGF受体）的双重阻断，以及类固醇激素拮抗剂和抗生长因子治疗的组合以最大化肿瘤抑制。
Experimental evidence suggests that human breast cancer cells can be regulated by the IGF-I and IGF-II present in the tumor stromal elements and/or by the endogenous tumor cell IGF-II in a paracrine or autocrine fashion. Thus, blockade of the receptor signalling pathway could lead to diminished tumor growth. Blockade of the type I IGF receptor by a monoclonal antibody (alpha-IR3) has been used as a strategy to demonstrate the importance of the IGF pathway. Although alpha-IR3 could not block serum-free growth of breast cancer cell lines, it could inhibit anchorage independent growth in most cell lines in the presence of serum. In vivo, alpha-IR3 administered at the time of tumor cell inoculation could inhibit MDA-MB-231 tumor formation in athymic mice; however, inhibition of established tumors was not seen. Moreover, alpha-IR3 could not inhibit tumor formation of the MCF-7 cell line in vivo. These results suggest that blockade of the type I IGF receptor can inhibit the growth of some breast cancer cells both in vitro and in vivo. Future anti-growth factor strategies include the combination of anti-IGF receptor antibodies with IGF neutralizing modalities, the dual blockade of growth factor receptors (epidermal growth factor receptor and type I IGF receptor), and combinations of steroid hormone antagonists and anti-growth factor treatments to maximize tumor inhibition.