|
|
S100A6 Promotes Cell Proliferation of Colorectal Cancer via Upregulating IL-6 Expression of Macrophages |
Lu CHEN,Mao HUANG,Qi PENG,Jia-li ZHAO,Jia-qing XIE,Lu LIN,Li-jun HU,Yi-yun HUANG,Qin HU,Lan ZHOU() |
Key Laboratory of Laboratory Medical Diagnostics of Ministry of Education, Chongqing Medical University, Chongqing 400016, China |
|
|
Abstract Objective: To explore whether Calcyclin S100A6 in tumor microenvironment promotes cell proliferation of colorectal cancer(CRC) through affecting macrophages (Mφ) and its mechanism. Methods: Prokaryotic expression was used to prepare recombinant human protein GST-S100A6 (rS100A6) and GST (as control). THP-1 were induced to Mφ by PMA (Phorbol-12-myristate-13-acetate). A6-Mφ were the macrophages which were treated with rS100A6 for 24h. The proliferation of CRC HCT116 cells was detected by Trypan blue staining, CCK8 and crystal violet staining. IL-6 mRNA and protein level in A6-Mφ were tested with quantitative polymerase chain reaction (qPCR) and Western blot, respectively. The protein levels of total JAK2 and STAT3 (t-JAK2 and t-STAT3) and the phosphorylated JAK2 and STAT3 (p-JAK2 and p-STAT3) in HCT116 cells were detected by Western blot. Results: (1) rS100A6 and GST were prepared successfully. (2) A6-Mφ promoted proliferation of HCT116 cells (P<0.05). (3) rS100A6 upregulated IL-6 expression in macrophages (P<0.05). (4) IL-6R blocking antibody partly reversed the facilitation of A6-Mφ to proliferation of HCT116 cells (P<0.05). (5) A6-Mφ increased protein levels of p-JAK2 and p-STAT3 in HCT116 cells (P<0.05), but not t-JAK2 and t-STAT3. Conclusion: S100A6 in tumor microenvironment facilitates proliferation of HCT116 cells through upregulating IL-6 expression in macrophages and activating IL-6/JAK2/STAT3 pathway in HCT116 cells.
|
Received: 06 September 2018
Published: 08 May 2019
|
|
Corresponding Authors:
Lan ZHOU
E-mail: zhoulan0111@foxmail.com
|
|
Cite this article:
Lu CHEN,Mao HUANG,Qi PENG,Jia-li ZHAO,Jia-qing XIE,Lu LIN,Li-jun HU,Yi-yun HUANG,Qin HU,Lan ZHOU. S100A6 Promotes Cell Proliferation of Colorectal Cancer via Upregulating IL-6 Expression of Macrophages. China Biotechnology, 2019, 39(4): 1-7.
URL:
https://manu60.magtech.com.cn/biotech/10.13523/j.cb.20190401 OR https://manu60.magtech.com.cn/biotech/Y2019/V39/I4/1
|
|
|
[1] |
Weitz J, Koch M, Debus J , et al. Colorectal cancer. Lancet, 2005,365(9454):153-165.
doi: 10.1016/S0140-6736(05)17706-X
|
|
|
[2] |
Komohara Y, Fujiwara Y, Ohnishi K , et al. Tumor-associated macrophages: Potential therapeutic targets for anti-cancer therapy. Advanced Drug Delivery Reviews, 2016,99(Pt B):180-185.
doi: 10.1016/j.addr.2015.11.009
pmid: 26621196
|
|
|
[3] |
Erreni M, Mantovani A, Allavena P . Tumor-associated macrophages (TAM) and inflammation in colorectal cancer. Cancer Microenvironment, 2011,4(2):141-154.
doi: 10.1007/s12307-010-0052-5
pmid: 3170420
|
|
|
[4] |
Nakayama Y, Nagashima N, Minagawa N , et al. Relationships between tumor-associated macrophages and clinicopathological factors in patients with colorectal cancer. Anticancer Research, 2002,22(6C):4291-4296.
doi: 10.1097/00001813-200211000-00011
pmid: 12553072
|
|
|
[5] |
Donato R, Sorci G, Giambanco I . S100A6 protein: Functional roles. Cellular & Molecular Life Sciences, 2017,74(4):2749-2760.
doi: 10.1007/s00018-017-2526-9
pmid: 28417162
|
|
|
[6] |
Duan L, Wu R, Zou Z , et al. S100A6 stimulates proliferation and migration of colorectal carcinoma cells through activation of the MAPK pathways. International Journal of Oncology, 2014,44(3):781-90.
doi: 10.3892/ijo.2013.2231
pmid: 243787491006
|
|
|
[7] |
Donato R, Cannon B R, Sorci G , et al. Functions of S100 proteins. Current Molecular Medicine, 2013,13(1):24-57.
doi: 10.2174/156652413804486214
|
|
|
[8] |
Byun K, Yoo Y, Son M , et al. Advanced glycation end-products produced systemically and by macrophages: A common contributor to inflammation and degenerative diseases. Pharmacology & Therapeutics, 2017,177:44-55.
doi: 10.1016/j.pharmthera.2017.02.030
pmid: 28223234
|
|
|
[9] |
Nasser M W, Qamri Z, Deol Y S , et al. S100A7 enhances mammary tumorigenesis through upregulation of inflammatory pathways. Cancer Research, 2012,72(3):604-615.
doi: 10.1158/0008-5472.CAN-11-0669
pmid: 22158945
|
|
|
[10] |
Nasser M W, Wani N, Ahirwar D K , et al. RAGE mediates S100A7-induced breast cancer growth and metastasis by modulating the tumor microenvironment. Cancer Research, 2015,75(6):974-985.
doi: 10.1158/0008-5472.CAN-14-2161
pmid: 4359968
|
|
|
[11] |
Chavakis T, Bierhaus A, Nawroth P P . RAGE (receptor for advanced glycation end products): A central player in the inflammatory response. Microbes Infection, 2004,6(13):1219-1225.
doi: 10.1016/j.micinf.2004.08.004
pmid: 15488742
|
|
|
[12] |
Duan L, Wu R, Zou Z , et al. S100A6 stimulates proliferation and migration of colorectal carcinoma cells through activation of the MAPK pathways. International Journal of Oncology, 2014,44(3):781-790.
doi: 10.3892/ijo.2013.2231
pmid: 243787491006
|
|
|
[13] |
Zha H, Sun H, Li X , et al. S100A8 facilitates the migration of colorectal cancer cells through regulating macrophages in the inflammatory microenvironment. Oncology Reports, 2016,36(1):279-290.
doi: 10.3892/or.2016.4790
pmid: 27176480
|
|
|
[14] |
Forman D, Ferlay J, Jemal A , et al. Global cancer statistics. Ca A Cancer Journal for Clinicians, 2015,65(2):87-108.
doi: 10.3322/caac.21262
|
|
|
[15] |
Kampan N C, Xiang S D, Mcnally O M , et al. Immunotherapeutic interleukin-6 or interleukin-6 receptor blockade in cancer: Challenges and opportunities. Current Medicinal Chemistry, 2018,25(36):1-22.
doi: 10.2174/092986732501180122140757
|
|
|
[16] |
Wang H, Zhang L, Zhang I Y , et al. S100B promotes glioma growth through chemoattraction of myeloid-derived macrophages. Clinical Cancer Research, 2013,19(14):3764-3775.
doi: 10.1158/1078-0432.CCR-12-3725
pmid: 23719262
|
|
|
[17] |
Wunderlich C M, Ackermann P J, Ostermann A L , et al. Obesity exacerbates colitis-associated cancer via IL-6-regulated macrophage polarisation and CCL-20/CCR-6-mediated lymphocyte recruitment. Nature Communication, 2018,9(1):1646.
doi: 10.1038/s41467-018-03773-0
|
|
|
[18] |
Waldner M J, Sebastian F, Neurath M F . Interleukin-6-A key regulator of colorectal cancer development. International Journal of Biological Sciences, 2012,8(9):1248-1253.
doi: 10.7150/ijbs.4614
pmid: 3491448
|
|
|
|
Viewed |
|
|
|
Full text
|
|
|
|
|
Abstract
|
|
|
|
|
Cited |
|
|
|
|
|
Shared |
|
|
|
|
|
Discussed |
|
|
|
|