Bone marrow-derived mesenchymal stem cells promote growth and angiogenesis of breast and prostate tumors.
Bone marrow-derived mesenchymal stem cells promote growth and angiogenesis of breast and prostate tumors.
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骨髓间充质干细胞促进乳腺和前列腺肿瘤的生长和血管生成
DOI：
10.1186/scrt221
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发表时间：
2013-06-13
影响因子：
7.5
通讯作者：
Li G
中科院分区：
文献类型：
--
作者：
Zhang T;Lee YW;Rui YF;Cheng TY;Jiang XH;Li G
简介已知间充质干细胞 (MSC) 会迁移到肿瘤组织。间充质干细胞的这种行为已被用作基于细胞的癌症治疗的肿瘤靶向策略。然而，间充质干细胞对肿瘤生长的影响存在争议。本研究旨在确定间充质干细胞对乳腺和前列腺肿瘤生长的影响。方法分离并表征骨髓源性间充质干细胞（BM-MSCs）。在与小鼠乳腺癌细胞 4T1 或人前列腺癌细胞 DU145 共培养系统中分析 BM-MSC 对肿瘤细胞增殖的影响。将肿瘤细胞单独或与 BM-MSC 联合皮下注射到裸鼠体内。免疫荧光分析肿瘤组织中细胞增殖和血管生成相关蛋白的表达。使用管形成试验检测 BM-MSC 的血管生成作用。通过免疫荧光和实时PCR检测肿瘤细胞与BM-MSCs之间的串扰对血管生成相关标志物表达的影响。结果与小鼠BM-MSCs（mBM-MSCs）共培养和mBM-MSC条件培养基处理均增强了4T1细胞的生长。与单独注射4T1细胞相比，将4T1细胞和mBM-MSCs共同注射到裸鼠体内导致肿瘤尺寸增加。使用 DU145 细胞和人 BM-MSC (hBM-MSC) 代替 4T1 细胞和 mBM-MSC 进行类似实验，获得了一致的结果。与单独注射肿瘤细胞诱导的肿瘤相比，共注射肿瘤细胞与BM-MSCs诱导的肿瘤的血管面积更大，这与中央肿瘤坏死减少和肿瘤细胞增殖增加相关。此外，单独hBM-MSCs的条件培养基以及hBM-MSCs与DU145细胞的共培养均能够促进人脐静脉内皮细胞的管形成能力。当hBM-MSC暴露于DU145细胞环境时，与新生血管形成相关的标志物（巨噬细胞炎症蛋白-2、血管内皮生长因子、转化生长因子-β和IL-6）的表达增加。结论这些结果表明BM-MSC促进肿瘤生长，并表明肿瘤细胞和BM-MSC之间的串扰增加了促血管生成因子的表达，这可能诱导肿瘤细胞增殖和血管生成，从而增加实体瘤的生长。
IntroductionMesenchymal stem cells (MSCs) are known to migrate to tumor tissues. This behavior of MSCs has been exploited as a tumor-targeting strategy for cell-based cancer therapy. However, the effects of MSCs on tumor growth are controversial. This study was designed to determine the effect of MSCs on the growth of breast and prostate tumors.MethodsBone marrow-derived MSCs (BM-MSCs) were isolated and characterized. Effects of BM-MSCs on tumor cell proliferation were analyzed in a co-culture system with mouse breast cancer cell 4T1 or human prostate cancer cell DU145. Tumor cells were injected into nude mice subcutaneously either alone or coupled with BM-MSCs. The expression of cell proliferation and angiogenesis-related proteins in tumor tissues were immunofluorescence analyzed. The angiogenic effect of BM-MSCs was detected using a tube formation assay. The effects of the crosstalk between tumor cells and BM-MSCs on expression of angiogenesis related markers were examined by immunofluorescence and real-time PCR.ResultsBoth co-culturing with mice BM-MSCs (mBM-MSCs) and treatment with mBM-MSC-conditioned medium enhanced the growth of 4T1 cells. Co-injection of 4T1 cells and mBM-MSCs into nude mice led to increased tumor size compared with injection of 4T1 cells alone. Similar experiments using DU145 cells and human BM-MSCs (hBM-MSCs) instead of 4T1 cells and mBM-MSCs obtained consistent results. Compared with tumors induced by injection of tumor cells alone, the blood vessel area was greater in tumors from co-injection of tumor cells with BM-MSCs, which correlated with decreased central tumor necrosis and increased tumor cell proliferation. Furthermore, both conditioned medium from hBM-MSCs alone and co-cultures of hBM-MSCs with DU145 cells were able to promote tube formation ability of human umbilical vein endothelial cells. When hBM-MSCs are exposed to the DU145 cell environment, the expression of markers associated with neovascularization (macrophage inflammatory protein-2, vascular endothelial growth factor, transforming growth factor-beta and IL-6) was increased.ConclusionThese results indicate that BM-MSCs promote tumor growth and suggest that the crosstalk between tumor cells and BM-MSCs increased the expression of pro-angiogenic factors, which may have induced tumor cell proliferation and angiogenesis thereby increasing solid tumor growth.
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影响因子：
7.5
作者：
Gharaibeh B;Lavasani M;Cummins JH;Huard J
通讯作者：
Huard J
DOI：
10.1158/1078-0432.ccr-11-1916
发表时间：
2012-02-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Klopp AH;Zhang Y;Solley T;Amaya-Manzanares F;Marini F;Andreeff M;Debeb B;Woodward W;Schmandt R;Broaddus R;Lu K;Kolonin MG
通讯作者：
Kolonin MG
影响因子：
15.9
作者：
McLean, Karen;Gong, Yusong;Buckanovich, Ronald J.
通讯作者：
Buckanovich, Ronald J.
DOI：
10.1073/pnas.0900244106
发表时间：
2009-03-10
影响因子：
11.1
作者：
Coffelt, Seth B.;Marini, Frank C.;Scandurro, Aline B.
通讯作者：
Scandurro, Aline B.
影响因子：
5.2
作者：
Klopp, Ann H.;Gupta, Anshul;Spaeth, Erika;Andreeff, Michael;Marini, Frank, III
通讯作者：
Marini, Frank, III