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Mol Cancer Ther.:新单抗能够抑制乳腺癌和血管肉瘤的癌细胞生长

  1. SFPR2
  2. 乳腺癌
  3. 单抗
  4. 血管肉瘤

来源:生物谷 2013-04-21 22:47

2013年4月21日 讯 /生物谷BIOON/ --北卡大学科学家发现一种单克隆抗体能够针对SFPR2蛋白在临床前模型中能够抑制乳腺癌和血管肉瘤癌细胞生长。相关报道发表在四月十九日的Molecular Cancer Therapeutics杂志上。 SFRP2蛋白表达在三阴乳腺癌和恶性血管肉瘤的癌细胞表面。

2013年4月21日 讯 /生物谷BIOON/ --北卡大学科学家发现一种单克隆抗体能够针对SFPR2蛋白在临床前模型中能够抑制乳腺癌和血管肉瘤癌细胞生长。相关报道发表在四月十九日的Molecular Cancer Therapeutics杂志上。

SFRP2蛋白表达在三阴乳腺癌和恶性血管肉瘤的癌细胞表面。北卡大学综合癌症中心教授Nancy Klauber-DeMore博士领导的研究团队首次合成一种针对SFRP2蛋白的单克隆抗体。研究人员发现该单抗能够减少癌细胞生长速率。

DeMore博士称,我们发现针对SFRP2的单抗在临床前模型中能够抑制癌细胞生长,说明SFRP2是一个很好的治疗癌症的靶点。

DeMore博士实验室首次发现SFRP2在癌细胞生长中有重要作用,并开发出FDA认证的抗血管再生药物Avastin。Avastin针对的是蛋白VEGF,该蛋白能够促进新血管生成。尽管Avastin对某些癌症病人有效,但是并不是所有的癌细胞都对Avastin敏感。为了治疗对Avastin有抗性的癌症,DeMore博士开始寻找其他可能的用于临床的靶点。

DeMore博士称,我们之前在恶性乳腺癌中分离了血管,比较分离的血管与正常组织的不同,我们发现在恶性血管中大量蛋白过表达。其中之一就是SFRP2。

DeMore实验室进一步发现SFRP2蛋白表达着多种癌细胞中,如乳腺癌,前列腺癌,肺癌,胰腺癌,卵巢癌,结肠癌,肾癌和血管肉瘤等。DeMore博士与血管方面著名教授Cam Patterson博士, Ernest博士和 Hazel Craige博士合作,发现了SFRP2能够刺激血管合成。于是他们猜测针对SFRP2的药物能够抑制癌细胞生长。与Russ Mumper博士合作终于开发出了针对SFRP2的单抗。

DeMore博士称,该发现为药物开发提供了新的思路,我们在致力于开发出能够用于临床治疗的药物。(生物谷Bioon.com)

A Novel Monoclonal Antibody to Secreted Frizzled-Related Protein 2 Inhibits Tumor Growth

Emily Fontenot, Emma Rossi, Russell Mumper, Stephanie Snyder, Sharareh Siamakpour-Reihani, Ping Ma, Eleanor Hilliard, Bradley Bone, David Ketelsen, Charlene Santos, Cam Patterson, and Nancy Klauber-DeMore.

Secreted frizzled-related protein 2 (SFRP2) is overexpressed in human angiosarcoma and breast cancer and stimulates angiogenesis via activation of the calcineurin/NFATc3 pathway. There are conflicting reports in the literature as to whether SFRP2 is an antagonist or agonist of β-catenin. The aims of these studies were to assess the effects of SFRP2 antagonism on tumor growth and Wnt-signaling and to evaluate whether SFRP2 is a viable therapeutic target. The antiangiogenic and antitumor properties of SFRP2 monoclonal antibody (mAb) were assessed using in vitro proliferation, migration, tube formation assays, and in vivo angiosarcoma and triple-negative breast cancer models. Wnt-signaling was assessed in endothelial and tumor cells treated with SFRP2 mAb using Western blotting. Pharmacokinetic and biodistribution data were generated in tumor-bearing and nontumor-bearing mice. SFRP2 mAb was shown to induce antitumor and antiangiogenic effects in vitro and inhibit activation of β-catenin and nuclear factor of activated T-cells c3 (NFATc3) in endothelial and tumor cells. Treatment of SVR angiosarcoma allografts in nude mice with the SFRP2 mAb decreased tumor volume by 58% compared with control (P = 0.004). Treatment of MDA-MB-231 breast carcinoma xenografts with SFRP2 mAb decreased tumor volume by 52% (P = 0.03) compared with control, whereas bevacizumab did not significantly reduce tumor volume. Pharmacokinetic studies show the antibody is long circulating in the blood and preferentially accumulates in SFRP2-positive tumors. In conclusion, antagonizing SFRP2 inhibits activation of β-catenin and NFATc3 in endothelial and tumor cells and is a novel therapeutic approach for inhibiting angiosarcoma and triple-negative breast cancer

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