BCR：科学家靶向作用特殊蛋白或可阻断恶性癌症的扩散

  近日，发表在国际杂志Breast Cancer Research上的一篇研究论文中，来自英属哥伦比亚大学(University Of British Columbia)的研究人员通过研究揭示了，抑制一种名为足糖萼蛋白的蛋白标记物或可明显减缓小鼠机体中恶性肿瘤的的生长和转移，同时研究者还开发出了可以靶向作用足糖萼蛋白的抗体，这就会开发新型疗法来抑制癌症的发生提供了新的思路。
  研究者Kelly McNagny博士指出，实际上有效抑制癌细胞迁移及扩散至机体其它位点的能力，是治疗转移性癌症的一大难点；足糖萼蛋白和5%的乳腺癌、大部分的卵巢癌及结肠癌亚型等癌症的发病直接相关，研究者的早期研究结果显示，肿瘤中足糖萼蛋白的存在和疾病的进展及患者较差的预后直接相关。
  很多情况下，如果机体在原发性肿瘤部位存在特殊的标志物的话，机体就会更易于在后期出现较差的疾病预后；而本文的研究结果则揭示，足糖萼蛋白的表达可以增强肿瘤细胞向机体其它组织位点迁移的能力，而靶向抗体则可以对足糖萼蛋白进行抑制作用。
  本文的研究发现为后期研究者开发新型疗法抑制转移性癌症发病及发展提供了新的线索；研究者下一步计划检测他们的研究结果，包括他们开发的抗体所具有的毒理学研究等。（转化医学网360zhyx.com）
  以上为转化医学网原创翻译整理，谢绝转载。如需转载，请联系 info@360zhyx.com
转化医学网推荐的原文摘要：

Podocalyxin enhances breast tumor growth and metastasis and is a target for monoclonal antibody therapy
Breast Cancer Research     doi:10.1186/s13058-015-0562-7
Kimberly A Snyder1†, Michael R Hughes1†, Bradley Hedberg2, Jill Brandon2, Diana Canals Hernaez1, Peter Bergqvist2, Frederic Cruz2, Kelvin Po2, Marcia L Graves3, Michelle E Turvey4, Julie S Nielsen1, John A Wilkins5, Shaun R McColl4, John S Babcook2, Calvin D Roskelley3 and Kelly M McNagny1*
Introduction Podocalyxin (gene name PODXL) is a CD34-related sialomucin implicated in the regulation of cell adhesion, migration and polarity. Upregulated expression of podocalyxin is linked to poor patient survival in epithelial cancers. However, it is not known if podocalyxin has a functional role in tumor progression. Methods We silenced podocalyxin expression in the aggressive basal-like human (MDA-MB-231) and mouse (4T1) breast cancer cell-lines and also overexpressed podocalyxin in the more benign human breast cancer cell line, MCF-7. We evaluated how podocalyxin affects tumorsphere-formation in vitro and compared the ability of podocalxyin-deficient (shPODXL) and -replete cell lines to form tumors and metastasize using xenogenic- or syngeneic-transplant models in mice. Finally, in an effort to develop therapeutic treatments for systemic cancers, we generated a series of anti-human podocalyxin antibodies and screened these for their ability to inhibit tumor progression in xenografted mice. Results Although deletion of podocalyxin does not alter gross cell morphology and growth under standard (adherent) culture conditions, expression of PODXL is required for efficient formation of tumorspheres in vitro. Correspondingly, silencing podocalyxin resulted in attenuated primary tumor growth and invasiveness in mice and severely impaired the formation of distant metastases. Likewise, in competitive tumor engraftment assays where we injected a 50:50 mixture of control and shPODXL (short-hairpin RNA targeting PODXL) cells, we found that podocalyxin-deficient cells exhibit a striking decrease in the ability to form clonal tumors in the lung, liver, and bone marrow. Finally, to validate podocalyxin as a viable target for immunotherapy we screened a series of novel anti-human podocalyxin antibodies for their ability to inhibit tumor progression in vivo. One of these antibodies, PODOC1, potently blocked tumor growth and metastasis. Conclusions We show that podocalyxin plays a key role in the formation of primary tumors and distant tumor metastasis. In addition, we validate podocalyxin as potential target for monoclonal antibody therapy to inhibit primary tumor growth and systemic dissemination.