Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
BMC Cancer. 2011 Aug 17;11:357. doi: 10.1186/1471-2407-11-357.
Increased hemostatic activity is common in many cancer types and often causes additional complications and even death. Circumstantial evidence suggests that tissue factor pathway inhibitor-1 (TFPI) plays a role in cancer development. We recently reported that downregulation of TFPI inhibited apoptosis in a breast cancer cell line. In this study, we investigated the effects of TFPI on self-sustained growth and motility of these cells, and of another invasive breast cancer cell type (MDA-MB-231).
Stable cell lines with TFPI (both α and β) and only TFPIβ downregulated were created using RNA interference technology. We investigated the ability of the transduced cells to grow, when seeded at low densities, and to form colonies, along with metastatic characteristics such as adhesion, migration and invasion.
Downregulation of TFPI was associated with increased self-sustained cell growth. An increase in cell attachment and spreading was observed to collagen type I, together with elevated levels of integrin α2. Downregulation of TFPI also stimulated migration and invasion of cells, and elevated MMP activity was involved in the increased invasion observed. Surprisingly, equivalent results were observed when TFPIβ was downregulated, revealing a novel function of this isoform in cancer metastasis.
Our results suggest an anti-metastatic effect of TFPI and may provide a novel therapeutic approach in cancer.
在许多癌症类型中，止血活性增加是常见的，并且常常导致额外的并发症甚至死亡。间接证据表明组织因子途径抑制剂-1（TFPI）在癌症发展中起作用。我们最近报道 TFPI 的下调抑制了乳腺癌细胞系的细胞凋亡。在这项研究中，我们研究了 TFPI 对这些细胞以及另一种侵袭性乳腺癌细胞类型（MDA-MB-231）的自我维持生长和运动性的影响。
使用 RNA 干扰技术创建了具有 TFPI（α和β）和仅下调 TFPIβ 的稳定细胞系。我们研究了转导细胞在低密度接种时的生长能力和形成集落的能力，以及黏附、迁移和侵袭等转移特征。
TFPI 的下调与自我维持细胞生长的增加有关。观察到细胞对 I 型胶原的附着和扩展增加，同时整合素 α2 水平升高。TFPI 的下调还刺激了细胞的迁移和侵袭，并且观察到的侵袭增加涉及 MMP 活性的升高。令人惊讶的是，当下调 TFPIβ 时观察到等效的结果，揭示了该同工型在癌症转移中的新功能。
我们的结果表明 TFPI 具有抗转移作用，并且可能为癌症提供新的治疗方法。
