Department of Thyroid and Breast Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, China.
Department of Thyroid and Breast Surgery, Guang'an City People's Hospital, Guang'an, Sichuan, China.
Clin Transl Oncol. 2022 Nov;24(11):2136-2145. doi: 10.1007/s12094-022-02865-0. Epub 2022 Jul 1.
To investigate the subcellular localization of ANXA2 in breast cancer of different cell densities in humans and its relationship with the clinicopathological features of patients. To investigate the differences in ANXA2 subcellular localization in MDA-MB-231 cells of different cell densities. To compare the proliferation, invasion, and migration ability of MDA-MB-231 cells under different ANXA2 subcellular localization.
Immunohistochemistry was applied to detect the subcellular localization of ANXA2 in tissue sections of 60 breast cancer patients, and the association with ANXA2 subcellular localization was verified in conjunction with cell density. To investigate the relationship between cell density and clinicopathological data of breast cancer patients. To establish high- and low-density models of MDA-MB-231 breast cancer cell lines and verify the subcellular localization of ANXA2 using immunofluorescence and observation under confocal microscopy. The proliferation, migration, and invasion ability of MDA-MB-231 cells under different subcellular localization of ANXA2 were detected and compared using CCK-8 assay and Transwell assay. After changing the subcellular localization of ANXA2 in high-density MDA-MB-231 cells with PY-60, changes in biological behaviors of the compared MDA-MB-231 cells were observed. Two different 4T1 cell lines with high and low densities were implanted subcutaneously in nude mice to observe the effects of different cell densities on tumor growth in nude mice.
The clinical data showed that breast cancer with high cell density had higher T stage and higher TNM stage, and the cell density was positively correlated with breast cancer mass size. ANXA2 was mainly localized to the cell membrane when the cell density of breast cancer cells was high and to the cytoplasm when the cell density was low. The CCK-8 assay showed that the proliferation rate of MDA-MB-231 cells increased (P < 0.05) after shifting the subcellular localization of ANXA2 from the cell membrane to the cytoplasm. Transwell invasion assay and Transwell migration assay showed that the invasion and migration ability of MDA-MB-231 cells increased significantly after the subcellular localization of ANXA2 was transferred from the cell membrane to the cytoplasm (P < 0.05). The animal experiments showed that high-density breast cancer cells could promote the growth of subcutaneous tumors in nude mice relative to low-density breast cancer cells.
Cell density can regulate the subcellular localization of ANXA2, and changes in the subcellular localization of ANXA2 are accompanied by the changes in the biological behavior of breast cancer.
研究不同细胞密度的人乳腺癌中 ANXA2 的亚细胞定位及其与患者临床病理特征的关系。研究 MDA-MB-231 细胞在不同细胞密度下 ANXA2 亚细胞定位的差异。比较不同 ANXA2 亚细胞定位下 MDA-MB-231 细胞的增殖、侵袭和迁移能力。
应用免疫组织化学检测 60 例乳腺癌患者组织切片中 ANXA2 的亚细胞定位，并结合细胞密度验证 ANXA2 亚细胞定位的相关性。研究细胞密度与乳腺癌患者临床病理资料的关系。建立 MDA-MB-231 乳腺癌细胞系的高、低密度模型，并通过免疫荧光和共聚焦显微镜观察验证 ANXA2 的亚细胞定位。用 CCK-8 法和 Transwell 法检测不同 ANXA2 亚细胞定位下 MDA-MB-231 细胞的增殖、迁移和侵袭能力。用 PY-60 改变 MDA-MB-231 细胞高密度中的 ANXA2 亚细胞定位，观察比较 MDA-MB-231 细胞的生物学行为变化。将两种不同密度的 4T1 细胞系分别皮下植入裸鼠，观察不同细胞密度对裸鼠肿瘤生长的影响。
临床资料显示，细胞密度高的乳腺癌 T 分期和 TNM 分期较高，细胞密度与乳腺癌肿块大小呈正相关。当乳腺癌细胞密度较高时，ANXA2 主要定位于细胞膜，当细胞密度较低时，主要定位于细胞质。CCK-8 法显示，当 ANXA2 的亚细胞定位从细胞膜转移到细胞质时，MDA-MB-231 细胞的增殖率增加（P<0.05）。Transwell 侵袭实验和 Transwell 迁移实验显示，当 ANXA2 的亚细胞定位从细胞膜转移到细胞质时，MDA-MB-231 细胞的侵袭和迁移能力显著增强（P<0.05）。动物实验表明，与低密度乳腺癌细胞相比，高密度乳腺癌细胞可促进裸鼠皮下肿瘤的生长。
细胞密度可以调节 ANXA2 的亚细胞定位，而 ANXA2 的亚细胞定位改变伴随着乳腺癌生物学行为的改变。
