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Abstract
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.
Highlights
Breast cancer is the most commonly detected tumor in females and one of the leading causes of cancer-related death among women in the World [1]
We demonstrated that CD90 was highly expressed in the most aggressive basal-like breast tumor cell line (Hs578T), when compared with the non-tumorigenic one (MCF10A) or with the less aggressive lines (MDA-MB-231 and MDA-MB-435) [10], indicating that CD90 expression increased according to the malignancy degree of the cell lines, positively correlating to high malignancy grade in mammary carcinoma [9]
In order to assess the expression of CD90 in human breast cancer samples, we first used immunohistochemistry reactions in Tissue Microarray (TMA) slides, each containing ~300 fragments of tissues from a cohort of patients from the AC Camargo Cancer Hospital (São Paulo, Brazil) (S1 Table)
Summary
Breast cancer is the most commonly detected tumor in females and one of the leading causes of cancer-related death among women in the World [1]. The ductal carcinoma is evaluated according to the expression profile of the estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor type 2 receptor (HER2) and sub-classified into: hormone-positive receptors (luminal A, Luminal B), HER2-positive and triple negative for hormonal receptors (basal-like) [4]. Tumors expressing the hormone receptors (ER and PR) display the most favorable prognosis, relative to those which only display HER2 or those which do not express any of the three markers (triple negative) [5]. The triple negative basal-like subtype represents approximately 10–15% of all mammary carcinomas, being characterized by high histological grade, high mitotic index and low differentiation [6]. Several studies have been developed in the last few years, due to the lack of proper molecular targets, the diagnosis and treatment of patients with tumors of the basal-like phenotype is still limited and has been a major challenge [5, 8]
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