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人前列腺癌部位间充质干细胞(MSCs)的定量分析。

Quantification of Mesenchymal Stem Cells (MSCs) at sites of human prostate cancer.

作者信息

Brennen W Nathaniel, Chen Shuangling, Denmeade Samuel R, Isaacs John T

机构信息

Chemical Therapeutics Program, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.

出版信息

Oncotarget. 2013 Jan;4(1):106-17. doi: 10.18632/oncotarget.805.

Abstract

Circulating bone marrow-derived Mesenchymal Stem Cells (BM-MSCs) have an innate tropism for tumor tissue in response to the inflammatory microenvironment present in malignant lesions. The prostate is bombarded by numerous infectious and inflammatory insults over a lifetime. Chronic inflammation is associated with CXCL12, CCL5, and CCL2, which are highly overexpressed in prostate cancer. Among other cell types, these chemoattractant stimuli recruit BM-MSCs to the tumor. MSCs are minimally defined as plastic-adhering cells characterized by the expression of CD90, CD73, and CD105 in the absence of hematopoietic markers, which can differentiate into osteoblasts, chondrocytes, and adipocytes. MSCs are immunoprivileged and have been implicated in tumorigenesis through multiple mechanisms, including promoting proliferation, angiogenesis, and metastasis, in addition to the generation of an immunosuppressive microenvironment. We have demonstrated that MSCs represent 0.01-1.1% of the total cells present in core biopsies from primary human prostatectomies. Importantly, these analyses were performed on samples prior to expansion in tissue culture. MSCs in these prostatectomy samples are FAP-, CD90-, CD73-, and CD105-positive, and CD14-, CD20-, CD34-, CD45-, and HLA-DR-negative. Additionally, like BM-MSCs, these prostate cancer-derived stromal cells (PrCSCs) were shown to differentiate into osteoblasts, adipocytes and chondrocytes. In contrast to primary prostate cancer-derived epithelial cells, fluorescently-labeled PrCSCs and BM-MSCs were both shown to home to CWR22RH prostate cancer xenografts following IV injection. These studies demonstrate that not only are MSCs present in sites of prostate cancer where they may contribute to carcinogenesis, but these cells may also potentially be used to deliver cytotoxic or imaging agents for therapeutic and/or diagnostic purposes.

摘要

循环中的骨髓间充质干细胞(BM-MSCs)会因恶性病变中存在的炎症微环境而对肿瘤组织具有天然的趋向性。前列腺在一生中会受到无数感染性和炎症性刺激。慢性炎症与CXCL12、CCL5和CCL2相关,这些因子在前列腺癌中高度过表达。在其他细胞类型中,这些趋化因子刺激会将BM-MSCs招募至肿瘤部位。间充质干细胞被定义为可贴壁生长的细胞,其特征在于表达CD90、CD73和CD105,且不表达造血标志物,能够分化为成骨细胞、软骨细胞和脂肪细胞。间充质干细胞具有免疫特权,并且通过多种机制参与肿瘤发生,包括促进增殖、血管生成和转移,此外还能产生免疫抑制微环境。我们已经证明,间充质干细胞占原发性前列腺切除术中芯活检样本中总细胞的0.01 - 1.1%。重要的是,这些分析是在组织培养扩增之前对样本进行的。这些前列腺切除样本中的间充质干细胞FAP、CD90、CD73和CD105呈阳性,而CD14、CD20、CD34、CD45和HLA-DR呈阴性。此外,与BM-MSCs一样,这些前列腺癌来源的基质细胞(PrCSCs)也被证明能分化为成骨细胞、脂肪细胞和软骨细胞。与原发性前列腺癌来源的上皮细胞不同,静脉注射后,荧光标记的PrCSCs和BM-MSCs均显示归巢至CWR22RH前列腺癌异种移植瘤。这些研究表明,间充质干细胞不仅存在于前列腺癌部位并可能参与致癌过程,而且这些细胞还可能潜在地用于递送细胞毒性或成像剂以用于治疗和/或诊断目的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21b1/3702211/31962a35d84b/oncotarget-04-106-g001.jpg

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