Kidney cancer cells secrete IL-8 to activate Akt and promote migration of mesenchymal stem cells

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• 作者：Bi Liang-kuan ; M.D. ; Ph.D.^a ; ¹ ; Zhou Nan ; M.D.^b ; ¹ ; Liu Cheng ; M.D.^a ; ¹ ; Lu Fu-Ding ; M.D.^a ; Lin Tian-Xin ; M.D. ; Ph.D.^a ; Xuan Xu-Jun ; M.D. ; Ph.D.^a ; Jiang Chun ; M.D. ; Ph.D.^a ; Han Jin-Li ; M.D. ; Ph.D.^a ; Huang Hai ; M.D. ; Ph.D.^a ; Zhang Cai-Xia ; M.D. ; Ph.D.^a ; Dong Wen ; M.D.^a ; Liu Hao ; M.D.^a ; Huang Jian ; M.D. ; Ph.D.^a ; Xu Ke-Wei ; M.D. ; Ph.D.^a ; ^{xkw2005@163.com" class="auth_mail}
• 关键词：Kidney cancer ; Mesenchymal stem cell ; Interleukin-8 ; Extracellular signal-regulated protein kinase ; Akt
• 刊名：Urologic Oncology: Seminars and Original Investigations
• 出版年：July 2014
• 年：2014
• 卷：32
• 期：5
• 页码：607-612
• 全文大小：285 K

文摘

Mesenchymal stem cells (MSCs) are multipotent adult stem cells that have the capability of homing to cancer cells. Thus, MSCs play an important role in the development, metastasis, and drug resistance of cancers. The mechanisms underlying the homing of MSCs in kidney cancer are still poorly understood.

Methods

In the present study, enzyme-linked immunosorbent assay was used to measure the level of IL-8 in patients with kidney cancer and in the culture medium of kidney cancer cells. Immunofluorescence staining and reverse transcription polymerase chain reaction were utilized to explore the main receptor for IL-8 in MSCs. Transwell migration assay was performed to measure the migration ability of MSCs and Western blot test was performed to test the activation of signaling pathways.

Results

The serum level of IL-8 was markedly increased in patients with kidney cancer, and 2 kidney cancer cell lines were found to secrete IL-8. MSCs had high expression of the IL-8 receptor (CXCR2). Blocking IL-8 or CXCR2 could decrease the migration ability of MSCs. IL-8 could significantly increase Akt phosphorylation in MSCs.

Conclusions

Kidney cancer cells secrete IL-8 to activate the Akt signaling pathway via CXCR2 on MSCs, inducing the migration of MSCs, which may be one of the important mechanisms underlying the homing of MSCs in kidney cancer.