Fu Jing, Peng Shengkun
Department of Breast Surgery, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, Chengdu, Sichuan, 610000, China.
Department of Radiology, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, No. 32 of West Section 1st Ring Road, Chengdu, Sichuan, 610000, China.
Open Life Sci. 2023 Mar 3;18(1):20220510. doi: 10.1515/biol-2022-0510. eCollection 2023.
Triple-negative breast cancer (TNBC) is a subtype of breast cancer that exhibits aggressive tumor phenotypes, including rapid metastasis and tumor recurrence. Integrins belong to the family of transmembrane glycoproteins involved in regulating cell adhesion, proliferation, and differentiation through cell-cell and cell-extracellular matrix interactions. Aberrant β1 integrin signaling has been implicated in cancer invasion and metastasis processes. The present work aimed to investigate the role of β1 integrin in TNBC cancer progression using a mouse 4T1 cell line as a model system. We have sorted a subset of tumor-initiating cells (TICs) from the 4T1 cell line based on CD133 positivity by flow cytometry. RT-PCR and protein analysis studies showed the transcriptional upregulation of β1 integrin and its downstream target focal adhesion kinase in 4T1-TICs compared to parental 4T1 cells. In addition, the expression of β1 receptors in TICs is significantly higher than in parental population cells. Furthermore, cellular assays revealed that CD133 TICs have higher clonogenic ability, invasion, and sphere formation potential. These findings suggest that β1 integrin has a potential role in TNBC invasion and metastasis. Hence, β1 integrin could be a possible factor for future targeted cancer therapies.
三阴性乳腺癌（TNBC）是乳腺癌的一种亚型，具有侵袭性肿瘤表型，包括快速转移和肿瘤复发。整合素属于跨膜糖蛋白家族，通过细胞间和细胞与细胞外基质的相互作用参与调节细胞黏附、增殖和分化。异常的β1整合素信号传导与癌症侵袭和转移过程有关。本研究旨在以小鼠4T1细胞系为模型系统，研究β1整合素在TNBC癌症进展中的作用。我们通过流式细胞术根据CD133阳性从4T1细胞系中筛选出一部分肿瘤起始细胞（TICs）。逆转录-聚合酶链反应（RT-PCR）和蛋白质分析研究表明，与亲代4T1细胞相比，4T1-TICs中β1整合素及其下游靶点粘着斑激酶的转录上调。此外，TICs中β1受体的表达明显高于亲代群体细胞。此外，细胞试验表明，CD133 TICs具有更高的克隆形成能力、侵袭能力和球体形成潜力。这些发现表明，β1整合素在TNBC侵袭和转移中具有潜在作用。因此，β1整合素可能是未来靶向癌症治疗的一个潜在因素。
