VCAM-1 secreted from cancer-associated fibroblasts enhances the growth and invasion of lung cancer cells through AKT and MAPK signaling. (31st March 2020)

• Record Type: Journal Article
• Authors: Zhou, Zhuan; Zhou, Qin; Wu, Xia; Xu, San; Hu, Xiaohong; Tao, Xuxiu; Li, Bo; Peng, Jinwu; Li, Dan; Shen, Liangfang; Cao, Ya; Yang, Lifang
• Is Part Of: Cancer letters. Volume 473(2020)
• Page Start: 62
• Page End: 73
• Publication Date: 2020-03-31
• Subjects: Cancer-associated fibroblasts -- Vascular cell adhesion molecule-1 -- AKT -- MAPK -- Cancer invasion; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2019.12.039
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: 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 α4β1 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 (α-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. Highlights: VCAM-1secreted from cancer associated fibroblasts (CAFs) promotes lung cancer cells proliferation, migration and invasion. CAFs activated AKT and MAPK signaling via VCAM-1 receptor very-late antigen (VLA)-4 in lung cancer cells. VCAM-1 expression was associated with a poor prognosis in lung cancer patients.