Liu Jing, Shen Jia-Xin, Wu Hua-Tao, Li Xiao-Li, Wen Xiao-Fen, Du Cai-Wen, Zhang Guo-Jun
Chang Jiang Scholar's Laboratory/Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Breast Cancer, Shantou University Medical College, Shantou, Guangdong 515041, China.
Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China.
Discov Med. 2018 May;25(139):211-223.
Extracellular matrix (ECM) is an important component of tumor microenvironment and plays critical roles in cancer development and metastasis, in which collagen is the major structural protein. Collagen type I alpha 1 (COL1A1) is reportedly associated with the development of several human diseases. However, the functions and mechanisms of cellular expression of COL1A1 in breast cancer remain unknown. The purpose of this study is to investigate the cellular expression of COL1A1 in breast cancer cells and patients, and its role in the development and metastasis of breast cancer.
The immunofluorescence staining was used to identify the cellular location of COL1A1 in breast cancer cell lines. Real-time PCR was applied to measuring the mRNA levels of COL1A1 and genes of interest. Wound healing and transwell assay were performed to evaluate the effect of COL1A1 on metastasis of breast cancer cells. 97 patients with breast cancer were recruited in this study for evaluating the correlation of COL1A1 with survival and clinicopathological parameters.
COL1A1 was expressed in all examined breast cancer cells. Knockdown of COL1A1 inhibited metastasis of breast cancer cells, with a low-level of CXCR4, independent of the epithelial-mesenchymal transition (EMT) process. In patients with breast cancer, cellular expression of COL1A1 was associated with ER/PR expression and metastasis status. The increased COL1A1 level was associated with poor survival, especially in patients with ER+ breast cancer. Patients with a high-level of COL1A1 showed better cisplatin-based chemotherapy response.
Cellular expression of COL1A1 could promote breast cancer metastasis. COL1A1 is a new prognostic biomarker and a potential therapeutic target for breast cancer, especially in ER+ patients.
细胞外基质（ECM）是肿瘤微环境的重要组成部分，在癌症发展和转移中起关键作用，其中胶原蛋白是主要的结构蛋白。据报道，I型胶原蛋白α1（COL1A1）与多种人类疾病的发生有关。然而，COL1A1在乳腺癌中的细胞表达功能和机制仍不清楚。本研究旨在探讨COL1A1在乳腺癌细胞和患者中的细胞表达及其在乳腺癌发展和转移中的作用。
采用免疫荧光染色法鉴定COL1A1在乳腺癌细胞系中的细胞定位。应用实时PCR检测COL1A1及相关基因的mRNA水平。进行伤口愈合实验和Transwell实验以评估COL1A1对乳腺癌细胞转移的影响。本研究招募了97例乳腺癌患者，以评估COL1A1与生存及临床病理参数的相关性。
所有检测的乳腺癌细胞均表达COL1A1。敲低COL1A1可抑制乳腺癌细胞的转移，CXCR4水平降低，且与上皮-间质转化（EMT）过程无关。在乳腺癌患者中，COL1A1的细胞表达与ER/PR表达及转移状态相关。COL1A1水平升高与较差的生存率相关，尤其是在ER+乳腺癌患者中。COL1A1水平高的患者对基于顺铂的化疗反应较好。
COL1A1的细胞表达可促进乳腺癌转移。COL1A1是一种新的预后生物标志物，也是乳腺癌潜在的治疗靶点，尤其是在ER+患者中。
