Proteomic Molecular Portrait of Interface Zone in Breast Cancer
Proteomic Molecular Portrait of Interface Zone in Breast Cancer
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DOI：
10.1021/pr1004532
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发表时间：
2010-11-01
影响因子：
4.4
通讯作者：
Cho, Nam Hoon
中科院分区：
文献类型：
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作者：
Kang, Suki;Kim, Min Ju;Cho, Nam Hoon
手术肿瘤切缘旨在涵盖残留的肿瘤细胞，但可能并不总是准确地描绘肿瘤和正常组织之间的边界。基于分子分析确定肿瘤边缘的努力取得了有限的成功。此外，没有临床试验涉及肿瘤微环境的范围。在这里，我们考虑了肿瘤细胞群和周围的微环境在划定肿瘤边缘，乳腺癌分为肿瘤和正常区，并引入了界面区的概念，入侵的肿瘤前沿和正常组织之间的区域，在肿瘤侵袭和转移过程中通过重塑肿瘤微环境。肿瘤组织中侵袭标志物的病理特征在侵袭性肿瘤前沿内是最动态的。我们使用MALDI-MS比较了肿瘤、正常和界面区的蛋白质谱。通过肽质量指纹图谱鉴定界面区中上调的蛋白质，并通过化学辅助MALDI-PSD谱的数据库搜索确认。通过Western和免疫组织化学分析证实了RhoGDI α、CAPG、WDR 1和CK 8的上调。我们的研究结果表明，界面区的分子概况是独特的，并建议，上调蛋白质在这里可能与乳腺癌的进展和转移。
Surgical tumor margins are intended to encompass residual tumor cells but may not always accurately delineate the boundary between tumor and normal tissue. Efforts to define tumor margins based on molecular analysis have achieved limited success. Furthermore, no clinical trials have addressed the scope of the tumor microenvironment. Here, we considered the tumor cell population and surrounding microenvironment in delineating tumor margins, classifying breast cancer into tumor and normal zones, and introducing the concept of an interface zone, the region between the invading tumor front and normal tissue, which develops during tumor invasion and metastasis through remodeling of the tumor microenvironment. Pathological signatures of invasion markers in tumor tissues are most dynamic within the invading tumor front. We compared protein profiles of tumor, normal, and interface zones using MALDI-MS. Proteins upregulated in the interface zone were identified by peptide mass fingerprinting and confirmed by database searching with chemically assisted MALDI-PSD spectra. Upregulation was confirmed for RhoGDI alpha, CAPG, WDR1, and CK8 by Western and immunohistochemical analyses. Our results demonstrate that the molecular profile of the interface zone is unique and suggest that upregulation of proteins here may be related to progression and metastasis of breast carcinomas.