Jing Liu1, Jia-Xin Shen1,2, Hua-Tao Wu3, Xiao-Li Li1,4, Xiao-Fen Wen1,4, Cai-Wen Du1,4, Guo-Jun Zhang1,2. 1. Chang Jiang Scholar's Laboratory/Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Breast Cancer, Shantou University Medical College, Shantou, Guangdong 515041, China. 2. Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China. 3. Department of General Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China. 4. Department of Breast Medical Oncology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China.
Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
PURPOSE: 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. METHODS: 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. RESULTS: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. CONCLUSION: 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.
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