Expression of integrin α3β1 and cyclooxygenase-2 (COX2) are positively correlated in human breast cancer
Expression of integrin α3β1 and cyclooxygenase-2 (COX2) are positively correlated in human breast cancer
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DOI：
10.1186/1471-2407-14-459
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发表时间：
2014-06-20
期刊：
影响因子：
3.8
通讯作者：
DiPersio, C. Michael
中科院分区：
文献类型：
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作者：
Aggarwal, Anshu;Al-Rohil, Rami N.;DiPersio, C. Michael
背景：整合素 α 3 β 1 的表达与多种癌症（包括乳腺癌）的肿瘤进展、转移和不良预后相关。此外，临床前研究揭示了该整合素的重要促肿瘤发生和促转移功能，包括肿瘤生长、存活、侵袭和旁分泌诱导血管生成。我们之前发表的临床前乳腺癌模型研究表明，整合素 α 3 β 1 可以促进环氧合酶 2 (COX2/PTGS2) 的表达，而环氧合酶是乳腺癌进展的已知驱动因素。然而，这一调节的临床意义尚不清楚。本研究的目的是通过测试整合素 α 3 β 1 和 COX2 在各种形式的人类乳腺癌中的相关表达来评估整合素 α 3 β 1 和 COX2 之间关系的临床相关性。方法：采用免疫组织化学方法评估人类浸润性导管癌 (IDC) 样本中 α 3 和 COX2 的共表达，这些样本可以在商业组织微阵列上（n = 59 个样本），也可以从奥尔巴尼医疗中心档案中获得（n = 68 个样本）。对整合素 α 3 亚基或 COX2 的免疫染色强度进行评分，并进行 Spearman 等级相关系数分析，以评估它们在不同肿瘤亚型或临床病理标准之间和内部的共表达。结果：尽管整合素 α 3 或 COX2 的表达在临床 IDC 样本中存在差异，但在两种组织微阵列中检测到 α 3 和 COX2 之间存在统计学显着的正相关性 (r(s) = 0.49，p < 0.001，n = 59）和存档样本（r(s) = 0.59，p < 0.0001，n = 68）。在这两个样本集中，这种相关性与激素受体状态、组织学分级或疾病阶段无关。结论：COX2 和 α 3 在 IDC 中相关，与激素受体状态或其他临床病理特征无关，支持整合素 α 3 β 1 是人类乳腺癌中 COX2 表达的决定因素的假设。这些结果支持我们之前在乳腺癌细胞中报道的α3β1依赖性COX2基因表达的临床相关性。研究结果还表明，各种亚型的 COX2 阳性乳腺癌可能容易受到针对 α 3 β 1 的治疗策略的影响，并且 α 3 表达可能作为独立的预后生物标志物。
Background: Expression of integrin alpha 3 beta 1 is associated with tumor progression, metastasis, and poor prognosis in several cancers, including breast cancer. Moreover, preclinical studies have revealed important pro-tumorigenic and pro-metastatic functions for this integrin, including tumor growth, survival, invasion, and paracrine induction of angiogenesis. Our previously published work in a preclinical breast cancer model showed that integrin alpha 3 beta 1 promotes expression of cyclooxygenase-2 (COX2/PTGS2), a known driver of breast cancer progression. However, the clinical significance of this regulation was unknown. The objective of the current study was to assess the clinical relevance of the relationship between integrin alpha 3 beta 1 and COX2 by testing for their correlated expression among various forms of human breast cancer.Methods: Immunohistochemistry was performed to assess co-expression of alpha 3 and COX2 in specimens of human invasive ductal carcinoma (IDC), either on a commercial tissue microarray (n = 59 samples) or obtained from Albany Medical Center archives (n = 68 samples). Immunostaining intensity for the integrin alpha 3 subunit or COX2 was scored, and Spearman's rank correlation coefficient analysis was performed to assess their co-expression across and within different tumor subtypes or clinicopathologic criteria.Results: Although expression of integrin alpha 3 or COX2 varied among clinical IDC samples, a statistically significant, positive correlation was detected between alpha 3 and COX2 in both tissue microarrays (r(s) = 0.49, p < 0.001, n = 59) and archived samples (r(s) = 0.59, p < 0.0001, n = 68). In both sample sets, this correlation was independent of hormone receptor status, histological grade, or disease stage.Conclusions: COX2 and alpha 3 are correlated in IDC independently of hormone receptor status or other clinicopathologic features, supporting the hypothesis that integrin alpha 3 beta 1 is a determinant of COX2 expression in human breast cancer. These results support the clinical relevance of alpha 3 beta 1-dependent COX2 gene expression that we reported previously in breast cancer cells. The findings also suggest that COX2-positive breast carcinomas of various subtypes might be vulnerable to therapeutic strategies that target alpha 3 beta 1, and that alpha 3 expression might serve as an independent prognostic biomarker.