Markers of breast cancer stromal fibroblasts in the primary tumour site associated with lymph node metastasis: a systematic review including our case series.
Markers of breast cancer stromal fibroblasts in the primary tumour site associated with lymph node metastasis: a systematic review including our case series.
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DOI：
10.1042/bsr20130060
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发表时间：
2013-12-12
影响因子：
4
通讯作者：
Brentani MM
中科院分区：
文献类型：
--
作者：
Folgueira MA;Maistro S;Katayama ML;Roela RA;Mundim FG;Nanogaki S;de Bock GH;Brentani MM
CAF（癌症相关成纤维细胞）是乳腺癌基质中最丰富的细胞类型，产生大量趋化因子、生长因子和 ECM（细胞外基质）蛋白，可能有助于扩散和转移。腋窝淋巴结是乳腺癌的第一个转移部位；然而，迄今为止，对于 CAF 合成的哪些特定蛋白质可能与淋巴结受累有关，尚未达成共识。本研究的目的是对与区域转移相关的 CAF 生物标志物进行系统评价。 PubMed 的搜索词为：“乳腺癌”、“淋巴结”、成纤维细胞、间质或微环境。排除后，选择了八项评估 CAF 中生物标志物免疫表达和淋巴结状态的研究。这些研究中评估的生物标志物根据其本体论可分为两组：细胞外基质成分[MMP13（基质金属蛋白酶13）、TIMP2（金属蛋白酶组织抑制剂-2）、THBS1（血小板反应蛋白1）、LGALS1（凝集素，半乳糖苷结合，可溶性，1）]和对受伤的反应[PDPN （podoplanin）、PLAU（纤溶酶原激活剂、尿激酶）、PLAUR（纤溶酶原激活剂、尿激酶受体）、CAV1（小窝蛋白 1）、THBS1、LGALS1]。 CAF 中 MMP13 和 LGALS1 的阳性表达与区域转移的 OR（优势比）增强相关。相反，成纤维细胞的 CAV1 阳性染色与淋巴结受累的 OR 降低相关。通过免疫组织化学在一系列新的 65 个浸润性导管乳腺癌样本中进一步测试了 MMP13、PDPN 和 CAV1 的表达，未发现 CAF 中的生物标志物表达与淋巴结状态之间存在关联。有人认为乳腺癌亚型可能对 CAF 的行为产生不同的影响。评估这些生物标志物在不同肿瘤类型 CAF 中的预后意义将会很有趣。
CAFs (cancer-associated fibroblasts), the most abundant cell type in breast cancer stroma, produce a plethora of chemokines, growth factors and ECM (extracellular matrix) proteins, that may contribute to dissemination and metastasis. Axillary nodes are the first metastatic site in breast cancer; however, to the present date, there is no consensus of which specific proteins, synthesized by CAFs, might be related with lymph node involvement. The purpose of this study was to perform a systematic review of CAF biomarkers associated with the presence of regional metastasis. PubMed was searched using the words: ‘breast cancer’ and ‘lymph node’ and fibroblast or stroma or microenvironment. After exclusions, eight studies evaluating biomarkers immunoexpression in CAFs and lymph node status were selected. Biomarkers evaluated in these studies may be divided in two groups, according to their ontology: extracellular matrix components [MMP13 (matrix metalloproteinase 13), TIMP2 (tissue inhibitor of metalloproteinases-2), THBS1 (thrombospondin 1), LGALS1 (lectin, galactoside-binding, soluble, 1)] and response to wounding [PDPN (podoplanin), PLAU (plasminogen activator, urokinase), PLAUR (plasminogen activator, urokinase receptor), CAV1 (caveolin 1), THBS1, LGALS1]. A positive expression of MMP13 and LGALS1 in CAFs was associated with enhanced OR (odds ratio) for regional metastasis. Contrariwise, CAV1 positive staining of fibroblasts was associated with decreased OR for nodal involvement. Expression of MMP13, PDPN and CAV1 was further tested in a new series of 65 samples of invasive ductal breast carcinomas by immunohistochemistry and no association between biomarkers expression in CAFs and nodal status was found. It was suggested that breast cancer subtypes may differentially affect CAFs behaviour. It would be interesting to evaluate the prognostic significance of these biomarkers in CAFs from different tumour types.