转化生长因子-β（TGF-β）的阻断可抑制乳腺肿瘤细胞的活力、迁移和转移。
Blockade of TGF-beta inhibits mammary tumor cell viability, migration, and metastases.
作者信息
Muraoka Rebecca S, Dumont Nancy, Ritter Christoph A, Dugger Teresa C, Brantley Dana M, Chen Jin, Easterly Evangeline, Roebuck L Renee, Ryan Sarah, Gotwals Philip J, Koteliansky Victor, Arteaga Carlos L
机构信息
Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 27232, USA.
出版信息
J Clin Invest. 2002 Jun;109(12):1551-9. doi: 10.1172/JCI15234.
TGF-betas are potent inhibitors of epithelial cell proliferation. However, in established carcinomas, autocrine/paracrine TGF-beta interactions can enhance tumor cell viability and progression. Thus, we studied the effect of a soluble Fc:TGF-beta type II receptor fusion protein (Fc:TbetaRII) on transgenic and transplantable models of breast cancer metastases. Systemic administration of Fc:TbetaRII did not alter primary mammary tumor latency in MMTV-Polyomavirus middle T antigen transgenic mice. However, Fc:TbetaRII increased apoptosis in primary tumors, while reducing tumor cell motility, intravasation, and lung metastases. These effects correlated with inhibition of Akt activity and FKHRL1 phosphorylation. Fc:TbetaRII also inhibited metastases from transplanted 4T1 and EMT-6 mammary tumors in syngeneic BALB/c mice. Tumor microvessel density in a mouse dorsal skin window chamber was unaffected by Fc:TbetaRII. Therefore, blockade of TGF-beta signaling may reduce tumor cell viability and migratory potential and represents a testable therapeutic approach against metastatic carcinomas.
转化生长因子β（TGF-β）是上皮细胞增殖的强效抑制剂。然而，在已形成的癌中，自分泌/旁分泌TGF-β相互作用可增强肿瘤细胞的活力和进展。因此，我们研究了可溶性Fc：转化生长因子βII型受体融合蛋白（Fc：TβRII）对乳腺癌转移的转基因和可移植模型的影响。在MMTV-多瘤病毒中T抗原转基因小鼠中，全身给予Fc：TβRII不会改变原发性乳腺肿瘤的潜伏期。然而，Fc：TβRII增加了原发性肿瘤中的细胞凋亡，同时降低了肿瘤细胞的运动性、血管内渗和肺转移。这些作用与Akt活性和FKHRL1磷酸化的抑制相关。Fc：TβRII还抑制了同基因BALB/c小鼠中移植的4T1和EMT-6乳腺肿瘤的转移。小鼠背部皮肤窗口室中的肿瘤微血管密度不受Fc：TβRII的影响。因此，阻断TGF-β信号传导可能会降低肿瘤细胞的活力和迁移潜能，并代表一种针对转移性癌的可测试治疗方法。
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