Abstract：
OBJECTIVE: Previous studies have shown that cancer-associated fibroblasts (CAFs) may play a role in tumor growth and development through paracrine action. Several studies reported upregulated matrix metallopeptidase 1 (MMP1) expression in various cancers. The aim is to investigate the role of elevated MMP1 expression in CAFs of breast cancer.
METHODS: A total of 203 cases were used for immunohistochemical analysis based on multiple clinical parameters. Tissues for primary cultures of CAFs were collected from 10 breast cancer patients who underwent complete surgical resection of their tumors. MMP1 expression in primary CAFs was detected using reverse transcription-quantitative PCR and western blotting. MMP1-overexpressing CAFs were established via lentiviral transfection, followed by cell functional assays and animal xenograft experiments.
RESULTS: MMP1 expression in CAFs of breast cancer was significantly associated with T stage, triple-negative breast cancer status, neoadjuvant chemotherapy status and Ki67 expression. Additionally, MMP1 expression was closely correlated with unfavorable prognosis based on overall survival and disease-free survival analyses. Elevated MMP1 expression in CAFs was verified to promote cell adhesion, invasion, proliferation abilities and attenuate chemosensitivity to Taxotere treatment.
CONCLUSIONS: The results indicated that MMP1 expression in CAFs may participate in the malignant phenotype and unfavorable prognosis of breast cancer.
METHODS: A total of 203 cases were used for immunohistochemical analysis based on multiple clinical parameters. Tissues for primary cultures of CAFs were collected from 10 breast cancer patients who underwent complete surgical resection of their tumors. MMP1 expression in primary CAFs was detected using reverse transcription-quantitative PCR and western blotting. MMP1-overexpressing CAFs were established via lentiviral transfection, followed by cell functional assays and animal xenograft experiments.
RESULTS: MMP1 expression in CAFs of breast cancer was significantly associated with T stage, triple-negative breast cancer status, neoadjuvant chemotherapy status and Ki67 expression. Additionally, MMP1 expression was closely correlated with unfavorable prognosis based on overall survival and disease-free survival analyses. Elevated MMP1 expression in CAFs was verified to promote cell adhesion, invasion, proliferation abilities and attenuate chemosensitivity to Taxotere treatment.
CONCLUSIONS: The results indicated that MMP1 expression in CAFs may participate in the malignant phenotype and unfavorable prognosis of breast cancer.
摘要：
目的：先前的研究表明，癌症相关成纤维细胞（CAFs）可能通过旁分泌作用在肿瘤的生长和发展中发挥作用。一些研究报道了在各种癌症中上调的基质金属肽酶1(MMP1)表达。目的探讨MMP1表达升高在乳腺癌CAFs中的作用。
方法：共203例，根据多种临床参数进行免疫组化分析。从10例接受肿瘤完全手术切除的乳腺癌患者中收集用于CAF原代培养的组织。使用逆转录定量PCR和蛋白质印迹检测原代CAF中的MMP1表达。通过慢病毒转染建立了过表达MMP1的CAFs，随后进行细胞功能测定和动物异种移植实验。
结果：MMP1在乳腺癌CAFs中的表达与T分期显著相关，三阴性乳腺癌状态，新辅助化疗状态和Ki67表达。此外,根据总生存期和无病生存期分析，MMP1表达与不良预后密切相关。证实CAFs中MMP1表达升高可促进细胞粘附，入侵,增殖能力和减弱对泰索帝治疗的化学敏感性。
结论：结果表明，CAFs中MMP1的表达可能参与了乳腺癌的恶性表型和不良预后。
方法：共203例，根据多种临床参数进行免疫组化分析。从10例接受肿瘤完全手术切除的乳腺癌患者中收集用于CAF原代培养的组织。使用逆转录定量PCR和蛋白质印迹检测原代CAF中的MMP1表达。通过慢病毒转染建立了过表达MMP1的CAFs，随后进行细胞功能测定和动物异种移植实验。
结果：MMP1在乳腺癌CAFs中的表达与T分期显著相关，三阴性乳腺癌状态，新辅助化疗状态和Ki67表达。此外,根据总生存期和无病生存期分析，MMP1表达与不良预后密切相关。证实CAFs中MMP1表达升高可促进细胞粘附，入侵,增殖能力和减弱对泰索帝治疗的化学敏感性。
结论：结果表明，CAFs中MMP1的表达可能参与了乳腺癌的恶性表型和不良预后。
