Tang Zhuo, Yu Minghuan, Miller Fred, Berk Richard S, Tromp Gerard, Kosir Mary Ann
Department of Surgery, Wayne State University, Detroit, MI, USA.
Am J Surg. 2008 Nov;196(5):690-6. doi: 10.1016/j.amjsurg.2008.08.001.
CXC chemokines may modify breast cancer cells and surrounding extracellular matrix to facilitate metastasis. CXCL7 is heparin binding, has heparanase activity, and is a ligand to CXCR2, a G-protein-linked receptor.
Isogenic cell lines, malignant MCF10CA1a.cl1 cells, and premalignant MCF10AT cells were used. CXCR2 and CXCL7 expression levels were quantified by reverse transcriptionase-polymerase chain reaction and Western blot. MCF10AT cells were stably transfected with CXCL7, and matrigel invasion assays were performed. Antibody to CXCL7 was used to inhibit invasion. CXCL7 secretion by transfectants and heparanase activity were quantified by enzyme-linked immunosorbent assay.
CXCL7 and CXCR2 expression were significantly higher in malignant MCF10CA1a.cl1 cells than in premalignant MCF10AT cells. Secreted CXCL7, secreted heparanase activity, and invasiveness were all increased in CXCL7-transfected MCF10AT cells. CXCL7 antibody inhibited invasion of CXCL7-transfected MCF10AT cells.
Malignant MCF10CA1a.cl1 cells express more CXCL7 and CXCR2 than premalignant MCF10AT cells. CXCL7-transfected MCF10AT cells are as invasive as malignant breast cancer cells.
CXC趋化因子可改变乳腺癌细胞及周围细胞外基质，以促进转移。CXCL7可与肝素结合，具有乙酰肝素酶活性，是G蛋白偶联受体CXCR2的配体。
使用同基因细胞系、恶性MCF10CA1a.cl1细胞和癌前MCF10AT细胞。通过逆转录聚合酶链反应和蛋白质印迹法对CXCR2和CXCL7的表达水平进行定量。用CXCL7稳定转染MCF10AT细胞，并进行基质胶侵袭试验。使用CXCL7抗体抑制侵袭。通过酶联免疫吸附测定法对转染细胞分泌的CXCL7和乙酰肝素酶活性进行定量。
恶性MCF10CA1a.cl1细胞中CXCL7和CXCR2的表达明显高于癌前MCF10AT细胞。在转染CXCL7的MCF10AT细胞中，分泌的CXCL7、分泌的乙酰肝素酶活性和侵袭性均增加。CXCL7抗体抑制了转染CXCL7的MCF10AT细胞的侵袭。
恶性MCF10CA1a.cl1细胞比癌前MCF10AT细胞表达更多的CXCL7和CXCR2。转染CXCL7的MCF10AT细胞与恶性乳腺癌细胞具有相同的侵袭性。
