比利時(shí)科學(xué)家成功解密了一種新的防癌機(jī)制,。研究人員發(fā)現(xiàn)，利用HRG（富含組氨酸糖蛋白）可使異常的腫瘤血管正?；?，進(jìn)而防止腫瘤細(xì)胞轉(zhuǎn)移，提高化療效果,。
在人體中,，所有組織的生長(zhǎng)都需要通過(guò)血管來(lái)提供氧氣和營(yíng)養(yǎng)，但腫瘤生長(zhǎng)的速度遠(yuǎn)遠(yuǎn)超過(guò)正常組織,，并有較高的營(yíng)養(yǎng)需要,，因此,，腫瘤細(xì)胞開(kāi)始產(chǎn)生生長(zhǎng)因子，刺激新血管的生長(zhǎng),，由此造成血管形態(tài)異常,。異常的血管形態(tài)導(dǎo)致血流不暢，氧氣供應(yīng)減少,。而氧氣供給不足會(huì)使癌細(xì)胞發(fā)生轉(zhuǎn)移,，最終形成惡性腫瘤。此外,，血管形態(tài)異常也使抗癌藥物無(wú)法到達(dá)病灶,，使治療效果大大降低。
傳統(tǒng)的治療癌癥方法為抗血管生成療法,，主要致力于消除生長(zhǎng)因子,，結(jié)果卻加劇了腫瘤的轉(zhuǎn)移。正因?yàn)槿绱?，近年?lái)在抗血管生成療法中,，腫瘤血管正常化更加受到關(guān)注,。此外,，通過(guò)抑制生長(zhǎng)因子（PlGF）的抗生長(zhǎng)因子療法也正作為治療癌癥的新手段進(jìn)行測(cè)試。
維薩里研究中心的夏洛特·羅尼及其同事與來(lái)自布魯塞爾自由大學(xué)及瑞典的研究人員合作,，深入研究了HRG抗腫瘤活性及其機(jī)理,。實(shí)驗(yàn)結(jié)果表明，HRG這種分布在腫瘤間質(zhì)的蛋白質(zhì)可防止腫瘤生長(zhǎng)和擴(kuò)散,，刺激腫瘤血管正?；Ｆ浠A(chǔ)是較大腫瘤有較高的氧氣需求,。然而，腫瘤血管的形狀異常,，導(dǎo)致血流不暢和氧氣供給不足,，缺氧刺激癌細(xì)胞轉(zhuǎn)移。HRG在控制腫瘤生長(zhǎng)和擴(kuò)散的同時(shí),，還可以抑制血管生長(zhǎng)因子（PlGF）,，進(jìn)而可以使異常的腫瘤血管恢復(fù)正常。
HRG抗癌新機(jī)制為癌癥治療開(kāi)辟了新的視野,，不僅能夠提高了化療療效,，還支持抗生長(zhǎng)因子療法，為治療癌癥提供了新思路和新手段,。（生物谷Bioon.com）
生物谷推薦原文出處：
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
