Breast stromal fibroblasts from histologically normal surgical margins are pro-carcinogenic.
Breast stromal fibroblasts from histologically normal surgical margins are pro-carcinogenic.
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DOI：
10.1002/path.4256
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发表时间：
2013-12
影响因子：
7.3
通讯作者：
Aboussekhra, Abdelilah
中科院分区：
文献类型：
--
作者：
Al-Rakan, Maha A.;Colak, Dilek;Hendrayani, Siti-Faujiah;Al-Bakheet, Albandary;Al-Mohanna, Falah H.;Kaya, Namik;Al-Malik, Osama;Aboussekhra, Abdelilah
有证据表明，正常乳腺基质成纤维细胞（NBFs）抑制肿瘤生长，而癌症相关成纤维细胞（CAFs）通过与肿瘤细胞的功能相互作用促进肿瘤发生。目前对组织学正常的手术切缘（TCF）中存在的间质成纤维细胞的生物学和致癌潜力知之甚少。因此，我们首先对来自乳腺癌患者的五个CAF/TCF对和三个NBF样本（来自乳房成形术）进行基因表达分析。这种比较分析揭示了这三类细胞之间基因表达的变化，具有TCF特异性基因表达谱。这种变异性在TCF中高于其配对的CAF和NBF。细胞因子阵列显示TCF具有特定的分泌细胞因子谱。此外，手术切缘的间质成纤维细胞表达高水平的α-SMA和SDF-1，并表现出更高的迁移/侵袭能力。间接共培养显示TCF细胞促进非癌乳腺上皮细胞的增殖和乳腺癌细胞的上皮向间质转化。此外，TCF和CAF细胞以旁分泌方式增加正常乳腺腔成纤维细胞中PCNA、MMP-2和Akt磷酸化/活化形式的水平。此外，TCF能够促进裸鼠人源化原位乳腺肿瘤的形成和生长。有趣的是，这些TCF表型及其影响程度介于NBFs和CAFs之间。总之，这些结果表明，位于非癌组织中的基质成纤维细胞表现出促肿瘤表型，表明它们在手术后的存在可能在癌症复发中起重要作用。© 2013作者。病理学杂志由John Wiley & Sons Ltd代表大不列颠和爱尔兰病理学会出版。
There is evidence that normal breast stromal fibroblasts (NBFs) suppress tumour growth, while cancer-associated fibroblasts (CAFs) promote tumourigenesis through functional interactions with tumour cells. Little is known about the biology and the carcinogenic potential of stromal fibroblasts present in histologically normal surgical margins (TCFs). Therefore, we first undertook gene expression analysis on five CAF/TCF pairs from breast cancer patients and three NBF samples (derived from mammoplasties). This comparative analysis revealed variation in gene expression between these three categories of cells, with a TCF-specific gene expression profile. This variability was higher in TCFs than in their paired CAFs and also NBFs. Cytokine arrays show that TCFs have a specific secretory cytokine profile. In addition, stromal fibroblasts from surgical margins expressed high levels of α-SMA and SDF-1 and exhibited higher migratory/invasiveness abilities. Indirect co-culture showed that TCF cells enhance the proliferation of non-cancerous mammary epithelial cells and the epithelial-to-mesenchymal transition of breast cancer cells. Moreover, TCF and CAF cells increased the level of PCNA, MMP-2 and the phosphorylated/activated form of Akt in normal breast luminal fibroblasts in a paracrine manner. Furthermore, TCFs were able to promote the formation and growth of humanized orthotopic breast tumours in nude mice. Interestingly, these TCF phenotypes and the extent of their effects were intermediate between those of NBFs and CAFs. Together, these results indicate that stromal fibroblasts located in non-cancerous tissues exhibit a tumour-promoting phenotype, indicating that their presence post-surgery may play important roles in cancer recurrence. © 2013 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
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影响因子：
8
作者：
Al-Ansari, M. M.;Hendrayani, S. F.;Shehata, A. I.;Aboussekhra, A.
通讯作者：
Aboussekhra, A.
影响因子：
--
作者：
Sadlonova, Andrea;Bowe, Damon B.;Frost, Andra R.
通讯作者：
Frost, Andra R.
影响因子：
19.7
作者：
Evans, Andrew;Whelehan, Patsy;Thompson, Alastair
通讯作者：
Thompson, Alastair
影响因子：
11.5
作者：
Belletti, Barbara;Vaidya, Jayant S.;Massarut, Samuele
通讯作者：
Massarut, Samuele
影响因子：
0.7
作者：
Aboussekhra, Abdelilah
通讯作者：
Aboussekhra, Abdelilah