基质细胞由结缔组织衍生而成,其会影响肿瘤的生长,维也纳医科大学的研究人员开发了一种新型技术,研究人员利用现代质谱法,通过穿刺组织样品进行检测就可以探知来自乳腺成纤维细胞中的肿瘤促进活性,相关研究发表于国际杂志Journal of Proteome Research上。

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长期以来科学家们熟知基质细胞会促进肿瘤生长,但是研究者们却很难理解是否是疾病间质状态保障了肿瘤的生长,或者说是肿瘤基质细胞主要引发了疾病间质状态的形成;我们机体的组织由多种类型细胞组成,这些细胞行使了不同的生物学功能,而乳腺组织的主要成分是上皮细胞和成纤维细胞,在乳腺癌中,当成纤维细胞改变其活性状态时上皮细胞也会发生转变,和癌症相关的成纤维细胞的典型活动类似于伤口愈合的过程。

文章中,研究人员利用现代质谱技术在第一阶段鉴别出了几千个不同的蛋白质,进一步研究发现,癌症中成纤维细胞可以表现出伤口愈合的活性,最终直接促进肿瘤的生长;而穿刺活检使得研究人员评估基质细胞的功能状态成为可能,Georg Pfeiler博士表示,目前我们仅可以利用血清来开发检测技术。

此外研究者们还将利用体外的动物模型来进行候选药物的检测,证实其是否可以进行预期细胞活性的干扰,而诸如新型疗法的临床应用或许可以真正改善当前疗法来预测个体的疾病风险及改善患者的生存质量。

原文摘要如下:

Proteome Profiling of Breast Cancer Biopsies Reveals a Wound Healing Signature of Cancer-Associated Fibroblasts

Breast cancer is still the most common type of cancer in women; an important role in carcinogenesis is actually attributed to cancer-associated fibroblasts. In this study, we investigated whether it is possible to assess the functional state of cancer-associated fibroblasts through tumor tissue proteome profiling. Tissue proteomics was performed on tumor-central, tumor-near, and tumor-distant biopsy sections from breast adenocarcinoma patients, which allowed us to identify 2074 proteins. Data were interpreted referring to reference proteome profiles generated from primary human mammary fibroblasts comprising 4095 proteins. These cells were analyzed in quiescent cell state as well as after in vitro treatment with TGFβ or IL-1β, stimulating wound healing or inflammatory processes, respectively. Representative for cancer cells, we investigated the mammary carcinoma cell line ZR-75-1, identifying 5212 proteins. All mass analysis data have been made fully accessible via ProteomeXchange, DOI PXD001311 and PXD001323-8. Comparison of tissue proteomics data with all of those reference profiles revealed predominance of cancer cell-derived proteins within the tumor and fibroblast-derived proteins in the tumor-distant tissue sections. Remarkably, proteins characteristic for acute inflammation were hardly identified in the tissue samples. In contrast, several proteins found by us to be induced by TGFβ in mammary fibroblasts, including fibulin-5, SLC2A1, and MUC18, were positively identified in all tissue samples, with relatively higher abundance in tumor neighboring tissue sections. These findings indicate a predominance of cancer-associated fibroblasts with wound healing activities localized around tumors.

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