比利时科学家成功解密了一种新的防癌机制。研究人员发现，利用HRG（富含组氨酸糖蛋白）可使异常的肿瘤血管正常化，进而防止肿瘤细胞转移，提高化疗效果。
在人体中，所有组织的生长都需要通过血管来提供氧气和营养，但肿瘤生长的速度远远超过正常组织，并有较高的营养需要，因此，肿瘤细胞开始产生生长因子，刺激新血管的生长，由此造成血管形态异常。异常的血管形态导致血流不畅，氧气供应减少。而氧气供给不足会使癌细胞发生转移，最终形成恶性肿瘤。此外，血管形态异常也使抗癌药物无法到达病灶，使治疗效果大大降低。
传统的治疗癌症方法为抗血管生成疗法，主要致力于消除生长因子，结果却加剧了肿瘤的转移。正因为如此，近年来在抗血管生成疗法中，肿瘤血管正常化更加受到关注。此外，通过抑制生长因子（PlGF）的抗生长因子疗法也正作为治疗癌症的新手段进行测试。
维萨里研究中心的夏洛特·罗尼及其同事与来自布鲁塞尔自由大学及瑞典的研究人员合作，深入研究了HRG抗肿瘤活性及其机理。实验结果表明，HRG这种分布在肿瘤间质的蛋白质可防止肿瘤生长和扩散，刺激肿瘤血管正常化。其基础是较大肿瘤有较高的氧气需求。然而，肿瘤血管的形状异常，导致血流不畅和氧气供给不足，缺氧刺激癌细胞转移。HRG在控制肿瘤生长和扩散的同时，还可以抑制血管生长因子（PlGF），进而可以使异常的肿瘤血管恢复正常。
HRG抗癌新机制为癌症治疗开辟了新的视野，不仅能够提高了化疗疗效，还支持抗生长因子疗法，为治疗癌症提供了新思路和新手段。（生物谷Bioon.com）
生物谷推荐原文出处：
Cancer Cell, 2011; DOI: 10.1016/j.ccr.2010.11.009
HRG Inhibits Tumor Growth and Metastasis by Inducing Macrophage Polarization and Vessel Normalization through Downregulation of PlGF
Ian Buysschaert2, 3, Johan Botling1, Uwe Himmelreich7, Jo A. Van Ginderachter4, 5, Michele De Palma6, Mieke Dewerchin2, 3, Lena Claesson-Welsh1, 11, , and Peter Carmeliet2, 3, 11
1 Uppsala University, Department of Genetics and Pathology, Rudbeck Laboratory, 75185 Uppsala, Sweden
2 Vesalius Research Center, VIB, Leuven, Belgium
3 Vesalius Research Center, K.U.Leuven, Leuven, Belgium
4 Laboratory of Cellular Molecular Immunology, Department Molecular Cellular Interactions, VIB, Brussels, Belgium
5 Laboratory of Cellular Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium
6 Angiogenesis & Tumor Targeting Unit, HSR-TIGET, and Vita-Salute University, San Raffaele Scientific Institute, 20132 Milan, Italy
7 MoSAIC, K.U. Leuven, Belgium
8 Uppsala University, Department Surgical Sciences, University Hospital, 75185 Uppsala
9 Uppsala University, Department Medical Cell Biology, Biomedical Center, Uppsala, Sweden
Received 13 February 2010; revised 12 August 2010; accepted 25 October 2010. Published online: January 6, 2011. Available online 6 January 2011.
Summary
Polarization of tumor-associated macrophages (TAMs) to a proangiogenic/immune-suppressive (M2-like) phenotype and abnormal, hypoperfused vessels are hallmarks of malignancy, but their molecular basis and interrelationship remains enigmatic. We report that the host-produced histidine-rich glycoprotein (HRG) inhibits tumor growth and metastasis, while improving chemotherapy. By skewing TAM polarization away from the M2- to a tumor-inhibiting M1-like phenotype, HRG promotes antitumor immune responses and vessel normalization, effects known to decrease tumor growth and metastasis and to enhance chemotherapy. Skewing of TAM polarization by HRG relies substantially on downregulation of placental growth factor (PlGF). Besides unveiling an important role for TAM polarization in tumor vessel abnormalization, and its regulation by HRG/PlGF, these findings offer therapeutic opportunities for anticancer and antiangiogenic treatment.
Highlights
HRG represses tumor growth and metastasis by macrophage polarization ? HRG-mediated macrophage polarization is dependent on suppression of PlGF ? HRG-mediated macrophage polarization promote immunomodulation ? Myeloid-derived PlGF monitors tumor vessel functionality and immune response
