Prospectively isolated cancer-associated CD10(+) fibroblasts have stronger interactions with CD133(+) colon cancer cells than with CD133(-) cancer cells.

Prospectively isolated cancer-associated CD10(+) fibroblasts have stronger interactions with CD133(+) colon cancer cells than with CD133(-) cancer cells.
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DOI:
10.1371/journal.pone.0012121
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发表时间:
2010-08-12
期刊:
影响因子:
3.7
通讯作者:
Tanaka M
Tanaka M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Cui L;Ohuchida K;Mizumoto K;Moriyama T;Onimaru M;Nakata K;Nabae T;Ueki T;Sato N;Tominaga Y;Tanaka M

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虽然CD 133已被报道是一种有前途的结肠癌干细胞标志物,但CD 133+结肠癌细胞的生物学功能仍存在争议。在本研究中,我们研究了CD 133+和CD 133 −结肠癌细胞之间的生物学差异,特别关注它们与癌症相关成纤维细胞,特别是CD 10+成纤维细胞的相互作用。我们使用了19个原发性结肠癌组织,30个来源于结肠癌组织的成纤维细胞的原代培养物和6个结肠癌细胞系。我们从结肠癌组织和培养细胞中分离出CD 133+和CD 133 −亚群。体外分析表明,两个群体在增殖和化疗敏感性方面表现出相似的生物学行为。体内分析显示,CD133+细胞的肿瘤生长显著大于CD133−细胞(P = 0.007)。  此外,在与来自结肠癌组织的原代成纤维细胞共培养中,CD 133+细胞表现出比CD 133 −细胞显著更强的侵袭行为(P<0.001),尤其是在与CD 10+成纤维细胞共培养中(P<0.0001)。进一步的体内分析显示,CD10+成纤维细胞促进CD133+细胞的肿瘤生长显著高于CD10−成纤维细胞(P<0.05)。这些数据表明,在特定的癌症相关的成纤维细胞,CD10+成纤维细胞的存在下,CD133+结肠癌细胞的体外侵袭特性和体内肿瘤生长得到增强,这表明这些特定细胞群之间的相互作用在癌症进展中具有重要作用。因此,这些特定的相互作用可能是新的结肠癌治疗的有前途的目标。
Although CD133 has been reported to be a promising colon cancer stem cell marker, the biological functions of CD133+ colon cancer cells remain controversial. In the present study, we investigated the biological differences between CD133+ and CD133− colon cancer cells, with a particular focus on their interactions with cancer-associated fibroblasts, especially CD10+ fibroblasts. We used 19 primary colon cancer tissues, 30 primary cultures of fibroblasts derived from colon cancer tissues and 6 colon cancer cell lines. We isolated CD133+ and CD133− subpopulations from the colon cancer tissues and cultured cells. In vitro analyses revealed that the two populations showed similar biological behaviors in their proliferation and chemosensitivity. In vivo analyses revealed that CD133+ cells showed significantly greater tumor growth than CD133− cells (P = 0.007). Moreover, in cocultures with primary fibroblasts derived from colon cancer tissues, CD133+ cells exhibited significantly more invasive behaviors than CD133− cells (P<0.001), especially in cocultures with CD10+ fibroblasts (P<0.0001). Further in vivo analyses revealed that CD10+ fibroblasts enhanced the tumor growth of CD133+ cells significantly more than CD10− fibroblasts (P<0.05). These data demonstrate that the in vitro invasive properties and in vivo tumor growth of CD133+ colon cancer cells are enhanced in the presence of specific cancer-associated fibroblasts, CD10+ fibroblasts, suggesting that the interactions between these specific cell populations have important roles in cancer progression. Therefore, these specific interactions may be promising targets for new colon cancer therapies.
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影响因子: 11.2
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发表时间: 2007-01-04
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影响因子: 64.8
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