Saaristo Anne, Karkkainen Marika J, Alitalo Kari
Molecular/Cancer Biology Laboratory, Biomedicum, University of Helsinki, Helsinki, Finland.
Ann N Y Acad Sci. 2002 Dec;979:94-110. doi: 10.1111/j.1749-6632.2002.tb04871.x.
Abnormal function of the lymphatic vessels is associated with a variety of diseases, such as tumor metastasis and lymphedema. The development of strategies for local and controlled induction or inhibition of lymphangiogenesis would thus be of major importance for the treatment of such diseases. Two growth factors, vascular endothelial growth factor C (VEGF-C) and D (VEGF-D), have been found to be important in the proper formation and maintenance of the lymphatic network, through their receptor VEGFR-3. In patients with lymphedema, heterozygous inactivation of VEGFR-3 leads to primary lymphedema due to defective lymphatic drainage in the limbs. We have shown that VEGF-C gene transfer to the skin of mice with lymphedema induces regeneration of the cutaneous lymphatic vessel network. However, as is the case with VEGF, high levels of VEGF-C cause blood vessel growth and leakiness, resulting in tissue edema. Strategies to avoid these side-effects have also been developed. This new field of reseach has important implications for the development of new therapies for human lymphedema.
淋巴管功能异常与多种疾病相关，如肿瘤转移和淋巴水肿。因此，制定局部且可控地诱导或抑制淋巴管生成的策略对于治疗此类疾病至关重要。已发现两种生长因子，即血管内皮生长因子C（VEGF-C）和D（VEGF-D），通过其受体VEGFR-3在淋巴管网络的正常形成和维持中发挥重要作用。在淋巴水肿患者中，VEGFR-3的杂合失活会因肢体淋巴引流缺陷导致原发性淋巴水肿。我们已表明，将VEGF-C基因转移至患有淋巴水肿的小鼠皮肤可诱导皮肤淋巴管网络再生。然而，与VEGF的情况一样，高水平的VEGF-C会导致血管生长和渗漏，从而引起组织水肿。避免这些副作用的策略也已被开发出来。这个新的研究领域对人类淋巴水肿新疗法的开发具有重要意义。
