Conti Ilaria, Dube Christine, Rollins Barrett J
Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02116, USA.
Novartis Found Symp. 2004;256:29-41; discussion 41-52, 266-9.
The chemokine system has evolved primarily to control the trafficking of leukocytes during immune or inflammatory responses. However, through their expression of chemokine ligands and receptors, cancers have commandeered various aspects of this host defence system in order to enhance their growth. Although engineered over-expression of some tumour-derived chemokines can stimulate host antitumour respones, this is unlikely to be the reason that tumour cells express them. Rather, a growing body of clinical and laboratory evidence indicates that cancer cells may secrete chemokines in order to attract host cells that supply the tumours with growth and angiogenic factors. In addition, chemokine receptor expression by tumour cells may permit them to use the host's pre-existing leukocyte trafficking system to invade target tissues during metastatic spread. Together, these observations suggest that therapies directed against chemokine ligands or receptors may be beneficial in cancer.
趋化因子系统主要进化为在免疫或炎症反应过程中控制白细胞的运输。然而,癌症通过趋化因子配体和受体的表达,征用了这个宿主防御系统的各个方面以促进自身生长。虽然一些肿瘤来源的趋化因子经工程改造后的过表达可刺激宿主的抗肿瘤反应,但这不太可能是肿瘤细胞表达它们的原因。相反,越来越多的临床和实验室证据表明,癌细胞可能分泌趋化因子以吸引为肿瘤提供生长和血管生成因子的宿主细胞。此外,肿瘤细胞上趋化因子受体的表达可能使它们能够利用宿主预先存在的白细胞运输系统在转移扩散过程中侵入靶组织。总之,这些观察结果表明,针对趋化因子配体或受体的疗法可能对癌症有益。