MCP-1/CCR-2 axis in adipocytes and cancer cell respectively facilitates ovarian cancer peritoneal metastasis

被引：70

作者：

Sun, Chaoyang ^{[1
]}

Li, Xi ^{[1
]}

Guo, Ensong ^{[1
]}

Li, Na ^{[1
,2
]}

Zhou, Bo ^{[1
,3
]}

Lu, Hao ^{[1
,4
]}

Huang, Jia ^{[1
]}

Xia, Meng ^{[1
,4
]}

Shan, Wanying ^{[1
]}

Wang, Beibei ^{[1
]}

Li, Kezhen ^{[1
]}

Weng, Danhui ^{[1
]}

Xu, Xiaoyan ^{[1
]}

Gao, Qinglei ^{[1
]}

Wang, Shixuan ^{[1
]}

Hu, Junbo ^{[1
,5
]}

Lu, Yiling ^{[6
]}

Mills, Gordon B. ^{[6
]}

Chen, Gang ^{[1
]}

机构：

[1] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Gynecol & Obstet, Wuhan 430030, Hubei, Peoples R China

[2] Peter MacCallum Canc Ctr, Canc Genet Lab, Melbourne, Vic 3000, Australia

[3] Wuhan Univ, Dept Gynecol Oncol, Zhongnan Hosp, Wuhan 430071, Hubei, Peoples R China

[4] Cent Hosp Wuhan, Dept Gynecol & Obstet, Wuhan 430030, Hubei, Peoples R China

[5] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Gastrointestinal Surg, Wuhan 430030, Hubei, Peoples R China

[6] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA

来源：

ONCOGENE | 2020年 / 39卷 / 08期

基金：

国家重点研发计划;

关键词：

MONOCYTE CHEMOATTRACTANT PROTEIN-1; CHEMOTACTIC PROTEIN-1; GENE-EXPRESSION; LIGAND; METFORMIN; RECEPTOR; GROWTH; OBESITY; CCL2; IDENTIFICATION;

D O I：

10.1038/s41388-019-1090-1

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Ovarian cancer selective metastasizes to the omentum contributing to the poor prognosis associated with ovarian cancer. However, the mechanism underlining this propensity and therapeutic approaches to counter this process has not been fully elucidated. Here, we show that MCP-1 produced by omental adipocytes binding to its cognate receptor CCR-2 on ovarian cancer cells facilitates migration and omental metastasis by activating the PI3K/AKT/mTOR pathway and its downstream effectors HIF-1 alpha and VEGF-A in cell lines, xenografts, and transgenic murine models. MCP-1 antibody significantly decreased tumor burden and increased survival of mice in vivo. Interestingly, metformin decreased omental metastasis at least partially by inhibiting MCP-1 secretion from adipocytes independent of direct effects on cancer cells. Together this suggests a novel target of MCP-1/CCR-2 axis that could benefit ovarian cancer patients.

引用

页码：1681 / 1695

页数：15

共 50 条

[1] Metformin prevents aggressive ovarian cancer growth driven by high-energy diet: similarity with calorie restriction [J].

Al-Wahab, Zaid ;

Mert, Ismail ;

Tebbe, Calvin ;

Chhina, Jasdeep ;

Hijaz, Miriana ;

Morris, Robert T. ;

Ali-Fehmi, Rouba ;

Giri, Shailendra ;

Munkarah, Adnan R. ;

Rattan, Ramandeep .

ONCOTARGET, 2015, 6 (13) :10908-10923

[2] Metformin Reduces Endogenous Reactive Oxygen Species and Associated DNA Damage [J].

Algire, Carolyn ;

Moiseeva, Olga ;

Deschenes-Simard, Xavier ;

Amrein, Lilian ;

Petruccelli, Luca ;

Birman, Elena ;

Viollet, Benoit ;

Ferbeyre, Gerardo ;

Pollak, Michael N. .

CANCER PREVENTION RESEARCH, 2012, 5 (04) :536-543

[3] Local Proliferation of Macrophages Contributes to Obesity-Associated Adipose Tissue Inflammation [J].

Amano, Shinya U. ;

Cohen, Jessica L. ;

Vangala, Pranitha ;

Tencerova, Michaela ;

Nicoloro, Sarah M. ;

Yawe, Joseph C. ;

Shen, Yuefei ;

Czech, Michael P. ;

Aouadi, Myriam .

CELL METABOLISM, 2014, 19 (01) :162-171

[4] Obesity and epithelial ovarian cancer survival: a systematic review and meta-analysis [J].

Bae, Hyo Sook ;

Kim, Hyun Jung ;

Hong, Jin Hwa ;

Lee, Jae Kwan ;

Lee, Nak Woo ;

Song, Jae Yun .

JOURNAL OF OVARIAN RESEARCH, 2014, 7

[5] Efficient and reproducible generation of tumour-infiltrating lymphocytes for renal cell carcinoma [J].

Baldan, V. ;

Griffiths, R. ;

Hawkins, R. E. ;

Gilham, D. E. .

BRITISH JOURNAL OF CANCER, 2015, 112 (09) :1510-1518

[6] New Strategies in the Treatment of Ovarian Cancer: Current Clinical Perspectives and Future Potential [J].

Banerjee, Susana ;

Kaye, Stanley B. .

CLINICAL CANCER RESEARCH, 2013, 19 (05) :961-968

[7] Integrated genomic analyses of ovarian carcinoma [J].

Bell, D. ;

Berchuck, A. ;

Birrer, M. ;

Chien, J. ;

Cramer, D. W. ;

Dao, F. ;

Dhir, R. ;

DiSaia, P. ;

Gabra, H. ;

Glenn, P. ;

Godwin, A. K. ;

Gross, J. ;

Hartmann, L. ;

Huang, M. ;

Huntsman, D. G. ;

Iacocca, M. ;

Imielinski, M. ;

Kalloger, S. ;

Karlan, B. Y. ;

Levine, D. A. ;

Mills, G. B. ;

Morrison, C. ;

Mutch, D. ;

Olvera, N. ;

Orsulic, S. ;

Park, K. ;

Petrelli, N. ;

Rabeno, B. ;

Rader, J. S. ;

Sikic, B. I. ;

Smith-McCune, K. ;

Sood, A. K. ;

Bowtell, D. ;

Penny, R. ;

Testa, J. R. ;

Chang, K. ;

Dinh, H. H. ;

Drummond, J. A. ;

Fowler, G. ;

Gunaratne, P. ;

Hawes, A. C. ;

Kovar, C. L. ;

Lewis, L. R. ;

Morgan, M. B. ;

Newsham, I. F. ;

Santibanez, J. ;

Reid, J. G. ;

Trevino, L. R. ;

Wu, Y. -Q. ;

Wang, M. .

NATURE, 2011, 474 (7353) :609-615

[8] Chemokine receptor CCR2 is expressed by human multiple myeloma cells and mediates migration to bone marrow stromal cell-produced monocyte chemotactic proteins MCP-1,-2 and-3 [J].

Broek, IV ;

Asosingh, K ;

Vanderkerken, K ;

Straetmans, N ;

Van Camp, B ;

Van Riet, I .

BRITISH JOURNAL OF CANCER, 2003, 88 (06) :855-862

[9]

Castadot P, 2005, Cancer Radiother, V9, P183, DOI 10.1016/j.canrad.2005.03.001

[10] CCL2/CCR2 Chemokine Signaling Coordinates Survival and Motility of Breast Cancer Cells through Smad3 Protein- and p42/44 Mitogen-activated Protein Kinase (MAPK)-dependent Mechanisms [J].

Fang, Wei Bin ;

Jokar, Iman ;

Zou, An ;

Lambert, Diana ;

Dendukuri, Prasanthi ;

Cheng, Nikki .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287 (43) :36593-36608

← 1 2 3 4 5 →