NUCEL (Cell and Molecular Therapy Center), Internal Medicine Department, School of Medicine, University of São Paulo, São Paulo, Brazil.
Biochemistry Department, Chemistry Institute, University of São Paulo, São Paulo, Brazil.
PLoS One. 2018 Jun 27;13(6):e0199254. doi: 10.1371/journal.pone.0199254. eCollection 2018.
Breast cancer is the most prevalent cancer among women, with the basal-like triple negative (TNBC) being the most agressive one, displaying the poorest prognosis within the ductal carcinoma subtype. Due to the lack of adequate molecular targets, the diagnosis and treatment of patients with the TNBC phenotype has been a great challenge. In a previous work, we identified CD90/Thy-1 as being highly expressed in the aggressive high malignancy grade Hs578T basal-like breast tumor cell line, pointing to this molecule as a promising breast tumor marker, which should be further investigated. Here, CD90 expression was analyzed in human breast cancer samples and its functional role was investigated to better assess the oncogenic nature of CD90 in mammary cells. Quantification of CD90 expression in human breast cancer samples, by tissue microarray, showed that high CD90 positivity correlates with metastasis and poor patient survival in the basal-like subtype. The functional genetic approach, by overexpression in the CD90 cDNA in a basal-like normal mammary cell line (MCF10A) and knockdown in a highly malignant cell line (Hs578T), allowed us to demonstrate that CD90 is involved with several cellular processes that lead to malignant transformation, such as: morphological change, increased cell proliferation, invasiveness, metastasis and activation of the EGFR pathway. Therefore, our results reveal that CD90 is involved with malignant transformation in breast cancer cell lines and is correlated with metastasis and poor patient survival in the basal-like subtype, being considered as a promising new breast cancer target.
乳腺癌是女性中最常见的癌症,基底样三阴性(TNBC)是最具侵袭性的一种,在导管癌亚型中预后最差。由于缺乏足够的分子靶点,TNBC 表型患者的诊断和治疗一直是一个巨大的挑战。在之前的工作中,我们发现 CD90/Thy-1 在侵袭性高恶性程度 Hs578T 基底样乳腺癌细胞系中高度表达,表明该分子是一种很有前途的乳腺癌标志物,值得进一步研究。在这里,我们分析了人乳腺癌样本中的 CD90 表达,并研究了其功能作用,以更好地评估 CD90 在乳腺细胞中的致癌性质。通过组织微阵列对人乳腺癌样本中 CD90 表达的定量分析表明,高 CD90 阳性与基底样亚型的转移和患者预后不良相关。通过在基底样正常乳腺细胞系(MCF10A)中过表达 CD90 cDNA 和在高度恶性细胞系(Hs578T)中敲低 CD90 的功能遗传方法,我们证明 CD90 参与了导致恶性转化的几个细胞过程,例如形态变化、细胞增殖增加、侵袭性、转移和 EGFR 途径的激活。因此,我们的结果表明 CD90 参与了乳腺癌细胞系的恶性转化,与基底样亚型的转移和患者预后不良相关,被认为是一种很有前途的新的乳腺癌治疗靶点。