VCAM-1 secreted from cancer-associated fibroblasts enhances the growth and invasion of lung cancer cells through AKT and MAPK signaling
VCAM-1 secreted from cancer-associated fibroblasts enhances the growth and invasion of lung cancer cells through AKT and MAPK signaling
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癌症相关成纤维细胞分泌的 VCAM-1 通过 AKT 和 MAPK 信号增强肺癌细胞的生长和侵袭
DOI：
10.1016/j.canlet.2019.12.039
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发表时间：
2020-01-01
期刊：
影响因子：
9.7
通讯作者：
Yang, Lifang
中科院分区：
文献类型：
--
作者：
Zhou, Zhuan;Zhou, Qin;Yang, Lifang
一些研究表明，癌症相关成纤维细胞（CAF）可以促进许多恶性肿瘤的癌症进展。然而，CAFs促进肺癌生长和转移的机制仍然不清楚。在本研究中，CAFs和正常成纤维细胞（NF）分离自人肺癌和癌旁组织。结果表明，CAFs的条件培养基（CM）能促进肺癌细胞的增殖、迁移和侵袭。血管细胞粘附分子-1（VCAM-1）在CAF-CM中的表达高于NF-CM，阻断VCAM-1可抑制肿瘤细胞的增殖和侵袭。此外，结果显示，在肺癌细胞中，从CAF分泌的VCAM-1通过受体α 4 β 1整联蛋白（极晚期抗原（VLA）-4）激活AKT和MAPK信号传导。此外，CAFs促进VCAM-1表达和体内肿瘤生长。此外，生物信息学分析表明CAF标志蛋白α-平滑肌肌动蛋白（α-SMA）和VCAM-1表达呈正相关，这与肺癌患者的预后不良有关。这些发现表明CAFs分泌的VCAM-1通过激活肺癌细胞的AKT和MAPK信号增强生长和侵袭。
Several studies have indicated that cancer-associated fibroblasts (CAFs) could promote cancer progression in many malignancies. However, the mechanism by which CAFs promote the growth and metastasis of lung cancer remains poorly defined. In the present study, CAFs and normal fibroblasts (NFs) were isolated from human lung cancer and adjacent tissue. The data showed that the conditional medium (CM) of CAFs could increase the proliferation, migration and invasion of lung cancer cells. Vascular cell adhesion molecule-1 (VCAM-1) showed a higher expression in CAF-CM than NF-CM, and blocking VCAM-1 in CAF-CM attenuated the proliferation and invasion of cancer cells. Further, the results showed that VCAM-1 secreted from CAFs activated AKT and MAPK signaling via receptor alpha 4 beta 1 integrin (very-late antigen (VLA)-4) in lung cancer cells. Moreover, CAFs promoted VCAM-1 expression and tumor growth in vivo. Additionally, bioinformatics analysis indicated a positive correlation on the CAF marker protein alpha-smooth muscle actin (alpha-SMA) and VCAM-1 expression, which was associated with a poor prognosis in lung cancer patients. These findings demonstrate that the VCAM-1 secreted from CAFs enhances growth and invasion by activating the AKT and MAPK signaling of lung cancer cells.