Int J Mol Sci:骨骼微环境中TGF-β信号对癌细胞和癌干细胞的影响

2020-04-24 MedSci原创 MedSci原创

转化生长因子-β(TGF-β)在骨转移形成中起着关键作用;我们假设TGF-β可能参与诱导骨微环境(micro-E)中的肿瘤干细胞(CSCs),这可能是化疗抗药性的原因。

转化生长因子-β(TGF-β)在骨转移形成中起着关键作用;我们假设TGF-β可能参与诱导骨微环境(micro-E)中的肿瘤干细胞(CSCs),这可能是化疗抗药性的原因。

将小鼠乳腺肿瘤细胞植入到雌性小鼠的乳腺背侧皮瓣下,并植入到雌性小鼠的皮下(subQ)病变处,在骨和subQ微环境(micro-Es)中产生肿瘤。植入肿瘤细胞后,用TGF-β R1激酶抑制剂(R1-KI)治疗小鼠。

结果显示,R1-Ki治疗降低了肿瘤体积和骨微-E中的细胞增殖,但在亚Q微-E中没有。R1-Ki治疗不影响骨或亚Q微-E中坏死或细胞凋亡的诱导。R1-Ki治疗后,骨小E中的CSC标志物SOX2和CD166阳性的细胞数量明显高于Q以下的小E。R1-KI治疗可显著减少骨小E中CSC标志物阳性细胞的数量,但在亚Q小E中则没有。MAPK/ERK和AKT通路的TGF-β激活是骨micro-E中细胞增殖的基础机制。BMP信号转导没有在细胞增殖中起作用。

综上所述,该研究结果表明,骨micro-E是CSC产生的关键利基,TGF-β信号转导在骨micro-E中产生CSCs和肿瘤细胞增殖中具有重要作用。因此,在体内不同的肿瘤微环境下,评估化疗药物对肿瘤干细胞和增殖的肿瘤细胞的反应至关重要。

原始出处:

Mitsuru FutakuchiKris Lami, et al., The Effects of TGF-β Signaling on Cancer Cells and Cancer Stem Cells in the Bone Microenvironment. Int J Mol Sci. 2019 Oct; 20(20): 5117. doi: 10.3390/ijms20205117

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    2020-07-02 changhe713
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    2020-04-27 独孤立克

    干细胞是热点,但是进入临床仍然需要时间和临床疗效验证哦

    0

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    2020-04-26 yxch36
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