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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Increased expression of preprotachykinin-l and neurokinin receptors in human breast cancer cells: lmplications for bone marrow metastasis
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Increased expression of preprotachykinin-l and neurokinin receptors in human breast cancer cells: lmplications for bone marrow metastasis

机译：前乳激肽原-1和神经激肽受体在人乳腺癌细胞中的表达增加：骨髓转移的意义

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摘要

Neuropeptides are implicated in many tumors, breast cancer (BC) included. Preprotachykinin-l (PPT-l) encodes multiple neuropep- tides with pleiotropic functions such as neurotransmission, im- mune/hematopoietic modulation, angiogenesis. and mitogenesis. PPT-l is constitutively expressed in some tumors. In this study, we investigated a role for PPT-l and its receptors. neurokinin-1 (NK-1) and NK-2, in BC by using quantitative reverse transcription--PCR. ELISA. and in situ hybridization. Compared with normal mammary epithelial cells (n = 2) and benign breast biopsies (n = 21). BC cell lines (n = 7) and malignant breast biopsies (n = 25) showed increased expression of PPT-l and NK-1. NK-2 levels were high in normal and malignant cells. Specific NK-1 and NK-2 antagonists inhibited BC cell proliferation. suggesting autocrine and/or inter- crine stimulation of BC cells by PPT-l peptides. NK-2 showed no effect on the proliferation of normal cells but mediated the proliferation of BC cells. Cytosolic extracts from malignant BC cells enhanced PPT-l translation whereas extracts from normal mam- mary epithelial cells caused no change. These enhancing effects may be protein-specific because a similar increase was observed for IL-6 translation and no effect was observed for IL-1 o and stem cell factor. The data suggest that PPT-l peptides and their receptors may be important in BC development. Considering that PPT-l peptides are hematopoietic modulators, these results could be extended to understand early integration of BC cells in the bone marrow, a preferred site of metastasis. Molecular signaling trans- duced by PPT-l peptides and the mechanism that enhances trans- lation of PPT-l mRNA could lead to innovative strategies for BC treatments and metastasis.
机译：神经肽与许多肿瘤有关，包括乳腺癌（BC）。前速激肽-1（PPT-1）编码具有多种功能的多种神经肽，如神经传递，免疫/造血调节，血管生成。和有丝分裂。 PPT-1在某些肿瘤中组成性表达。在这项研究中，我们研究了PPT-1及其受体的作用。定量逆转录PCR检测BC中的神经激肽-1（NK-1）和NK-2。 ELISA。和原位杂交。与正常乳腺上皮细胞（n = 2）和乳腺良性活检（n = 21）相比。 BC细胞系（n = 7）和恶性乳房活检（n = 25）显示PPT-1和NK-1表达增加。正常和恶性细胞中NK-2水平较高。特定的NK-1和NK-2拮抗剂抑制BC细胞增殖。提示通过PPT-1肽对BC细胞进行自分泌和/或间质刺激。 NK-2对正常细胞的增殖没有影响，但是介导了BC细胞的增殖。恶性BC细胞的胞质提取物增强了PPT-1的翻译，而正常哺乳动物上皮细胞的胞质提取物未引起变化。这些增强作用可能是蛋白质特异性的，因为对IL-6翻译观察到相似的增加，而对IL-1 o和干细胞因子未观察到任何作用。数据表明PPT-1肽及其受体在BC发展中可能是重要的。考虑到PPT-1肽是造​​血调节剂，可以扩展这些结果以了解BC细胞在骨髓中的早期整合，骨髓是转移的优选位点。 PPT-1肽转导的分子信号传导和增强PPT-1 mRNA转化的机制可能会导致创新的BC治疗和转移策略。

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