Dusp3 deletion in mice promotes experimental lung tumour metastasis in a macrophage dependent manner

[en] Vaccinia-H1 Related (VHR) dual-specificity phosphatase, or DUSP3, plays an important role in cell cycle regulation and its expression is altered in several human cancers. In mouse model, DUSP3 deletion prevents neo-angiogenesis and b-FGF-induced microvessel out- growth. Considering the importance of angiogenesis in metastasis formation, our study aimed to investigate the role of DUSP3 in tumour cell dissemination. Using a Lewis Lung carcinoma (LLC) experimental metastasis model, we observed that DUSP3-/- mice devel- oped larger lung metastases than littermate controls. DUSP3-/- bone marrow transfer to lethally irradiated DUSP3+/+ mice was sufficient to transfer the phenotype to DUSP3+/+ mice, indicating that hematopoietic cells compartment was involved in the increased tumour cell dissemination to lung tissues. Interestingly, we found a higher percentage of tumour- promoting Ly6Cint macrophages in DUSP3-/- LLC-bearing lung homogenates that was at least partially due to a better recruitment of these cells. This was confirmed by 1) the pres- ence of higher number of the Ly6Bhi macrophages in DUSP3-/- lung homogenates and by 2) the better migration of DUSP3-/- bone marrow sorted monocytes, peritoneal macrophages and bone marrow derived macrophages (BMDMs), compared to DUSP3+/+ monocytes, macrophages and BMDMs, in response to LLC-conditioned medium. Our study demon- strates that DUSP3 phosphatase plays a key role in metastatic growth through a mechanism involving the recruitment of macrophages towards LLC-bearing lungs.

Disciplines :

Oncology

Author, co-author :

Vandereyken, Maud

Jacques, Sophie ; Université de Liège - ULiège > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén.

Van Overmeire, Eva

Amand, Mathieu

Rocks, Natacha ; Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique

Delierneux, Celine

Singh, Pratibha

Singh, MAneesh

GHUYSEN, Camille ; Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service d'oncologie médicale

Wathieu, Caroline ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale

More authors (8 more)

Language :

English

Title :

Dusp3 deletion in mice promotes experimental lung tumour metastasis in a macrophage dependent manner

Publication date :

11 October 2017

Journal title :

PLoS ONE

eISSN :

1932-6203

Publisher :

Public Library of Science, San Franscisco, United States - California

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 12 November 2017

Statistics

Number of views

168 (48 by ULiège)

Number of downloads

109 (12 by ULiège)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

OpenAlex citations

publications

supporting

mentioning

contrasting

Smart Citations

Citing PublicationsSupportingMentioningContrasting

View Citations

See how this article has been cited at scite.ai

scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.

Bibliography

Ishibashi T, Bottaro DP, Chan A, Miki T, Aaronson SA. Expression cloning of a human dual-specificity phosphatase. Proc Natl Acad Sci U S A. 1992; 89: 12170–12174. https://doi.org/10.1073/pnas.89.24. 12170 PMID: 1281549
Yuvaniyama J., Denu J. M., Dixon J. E. & Saper MA. Crystal structure of the dual specificity protein phosphatase VHR. Science (80-). 1996; 272: 1328–1331.
Alonso a, Saxena M, Williams S, Mustelin T. Inhibitory role for dual specificity phosphatase VHR in T cell antigen receptor and CD28-induced Erk and Jnk activation. J Biol Chem. 2001; 276: 4766–71. https://doi.org/10.1074/jbc.M006497200 PMID: 11085983
Todd JL, Tanner KG, Denu JM. Extracellular Regulated Kinases (ERK) 1 and ERK2 Are Authentic Substrates for the Dual-specificity Protein-tyrosine Phosphatase. 1999; 274: 13271–13280. PMID: 10224087
Todd JL, Rigas JD, Rafty LA, Denu JM. Dual-specificity protein tyrosine phosphatase VHR down-regulates c-Jun N-terminal kinase (JNK). Oncogene. 2002; https://doi.org/10.1038/sj/onc/1205344
Nakamura K, Tanoue K, Satoh T, Takekawa M, Watanabe M, Shima H, et al. A novel low-molecular-mass dual-specificity phosphatase, LDP-2, with a naturally occurring substitution that affects substrate specificity. J Biochem. 2002; 132: 463–470. PMID: 12204117
Hoyt R, Zhu W, Cerignoli F, Alonso A, Mustelin T, David M. Cutting edge: selective tyrosine dephosphorylation of interferon-activated nuclear STAT5 by the VHR phosphatase. J Immunol. 2007; 179: 3402–6. https://doi.org/10.4049/jimmunol.179.6.3402 PMID: 17785772
Wang J-Y, Yeh C-L, Chou H-C, Yang C-H, Fu Y-N, Chen Y-T, et al. Vaccinia H1-related phosphatase is a phosphatase of ErbB receptors and is down-regulated in non-small cell lung cancer. J Biol Chem. 2011; 286: 10177–84. https://doi.org/10.1074/jbc.M110.163295 PMID: 21262974
Rahmouni S, Cerignoli F, Alonso A, Tsutji T, Henkens R, Zhu C, et al. Loss of the VHR dual-specific phosphatase causes cell-cycle arrest and senescence. Nat Cell Biol. 2006; 8: 524–531. https://doi.org/10.1038/ncb1398 PMID: 16604064
Henkens R, Delvenne P, Arafa M, Moutschen M, Zeddou M, Tautz L, et al. Cervix carcinoma is associated with an up-regulation and nuclear localization of the dual-specificity protein phosphatase VHR. BMC Cancer. 2008; 8: 147. https://doi.org/10.1186/1471-2407-8-147 PMID: 18505570
Arnoldussen YJ, Lorenzo PI, Pretorius ME, Waehre H, Risberg B, Maelandsmo GM, et al. The mitogen-activated protein kinase phosphatase vaccinia H1-related protein inhibits apoptosis in prostate cancer cells and is overexpressed in prostate cancer. Cancer Res. 2008; 68: 9255–64. https://doi.org/10.1158/0008-5472.CAN-08-1224 PMID: 19010898
Hao L, ElShamy WM. BRCA1-IRIS activates cyclin D1 expression in breast cancer cells by downregulating the JNK phosphatase DUSP3/VHR. Int J Cancer. 2007; 121: 39–46. https://doi.org/10.1002/ijc. 22597 PMID: 17278098
Wagner KW, Alam H, Dhar SS, Giri U, Li N, Wei Y, et al. Kdm2a promotes lung tumorigenesis by epigenetically enhancing erk1/2 signaling. J Clin Invest. 2013; 123: 5231–5246. https://doi.org/10.1172/ JCI68642 PMID: 24200691
Amand M, Erpicum C, Bajou K, Cerignoli F, Blacher S, Martin M, et al. DUSP3/VHR is a pro-angiogenic atypical dual-specificity phosphatase. Mol Cancer. 2014; 13: 108. https://doi.org/10.1186/1476-4598-13-108 PMID: 24886454
Joyce J a, Pollard JW. Microenvironmental regulation of metastasis. Nat Rev Cancer. 2009; 9: 239–52. https://doi.org/10.1038/nrc2618 PMID: 19279573
Zhu X-D, Zhang J-B, Zhuang P-Y, Zhu H-G, Zhang W, Xiong Y- Q, et al. High Expression of Macrophage Colony-Stimulating Factor-1 Receptor in Peritumoral Liver Tissue Is Associated with Poor Outcome in Hepatocellular Carcinoma After Curative Resection. J Clin Oncol. 2008; 26: 2707–2716. https://doi.org/10.1200/JCO.2007.15.6521 PMID: 18509183
Ryder M, Ghossein RA, Ricarte-Filho JCM, Knauf JA, Fagin JA. Increased density of tumor-associated macrophages is associated with decreased survival in advanced thyroid cancer. Endocr Relat Cancer. 2008; 15: 1069–1074. https://doi.org/10.1677/ERC-08-0036 PMID: 18719091
Galdiero MR, Bonavita E, Barajon I, Garlanda C, Mantovani A, Jaillon S. Tumor associated macrophages and neutrophils in cancer. Immunobiology. Elsevier GmbH.; 2013; 218: 1402–1410. https://doi.org/10.1016/j.imbio.2013.06.003 PMID: 23891329
Qian B- Z, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell. 2010; 141: 39–51. https://doi.org/10.1016/j.cell.2010.03.014 PMID: 20371344
Lewis CE, Pollard JW. Distinct role of macrophages in different tumor microenvironments. Cancer Res. 2006; 66: 605–612. https://doi.org/10.1158/0008-5472.CAN-05-4005 PMID: 16423985
Mantovani A, Sozzani S, Locati M, Allavena P, Sica A. Macrophage polarization: Tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol. 2002; 23: 549–555. https://doi.org/10.1016/S1471-4906(02)02302-5 PMID: 12401408
Laoui D, Van Overmeire E, Conza G Di, Aldeni C, Keirsse J, Morias Y, et al. Tumor hypoxia does not drive differentiation of tumor-associated macrophages but rather fine-tunes the M2-like macrophage population. Cancer Res. 2014; 74: 24–30. https://doi.org/10.1158/0008-5472.CAN-13-1196 PMID: 24220244
Singh P, Dejager L, Amand M, Theatre E, Vandereyken M, Zurashvili T, et al. DUSP3 Genetic Deletion Confers M2-like Macrophage-Dependent Tolerance to Septic Shock. J Immunol. 2015; 194: 4951–4962. https://doi.org/10.4049/jimmunol.1402431 PMID: 25876765
Movahedi K, Laoui D, Gysemans C, Baeten M, Stangé G, Van Bossche J Den, et al. Different tumor microenvironments contain functionally distinct subsets of macrophages derived from Ly6C(high) monocytes. Cancer Res. 2010; 70: 5728–5739. https://doi.org/10.1158/0008-5472.CAN-09-4672 PMID: 20570887
Mantovani A, Sica A. Macrophages, innate immunity and cancer: balance, tolerance, and diversity. Current Opinion in Immunology. 2010. pp. 231–237. https://doi.org/10.1016/j.coi.2010.01.009 PMID: 20144856
Dirkx AEM, Oude Egbrink MGA, Wagstaff J, Griffioen AW. Monocyte/macrophage infiltration in tumors: modulators of angiogenesis. J Leukoc Biol. 2006; 80: 1183–96. https://doi.org/10.1189/jlb.0905495 PMID: 16997855
Saigusa S, Inoue Y, Tanaka K, Toiyama Y, Okugawa Y, Shimura T, et al. Decreased expression of DUSP4 is associated with liver and lung metastases in colorectal cancer. Med Oncol. 2013; 30. https://doi.org/10.1007/s12032-013-0620-x PMID: 23749251
Wu S, Wang Y, Sun L, Zhang Z, Jiang Z, Qin Z, et al. Decreased expression of dual-specificity phosphatase 9 is associated with poor prognosis in clear cell renal cell carcinoma. BMC Cancer. BioMed Central Ltd; 2011; 11: 413. https://doi.org/10.1186/1471-2407-11-413 PMID: 21943117
Mathieu Amand, Charlotte Erpicum, Christine Gilles, Noel Agnes RS. functional analysis of dual specificity phosphatases in angiogenesis. Methods Mol Biol. 2016; 1447: 331–349. https://doi.org/10.1007/ 978-1-4939-3746-2_18 PMID: 27514814
Galaup A, Cazes A, Le Jan S, Philippe J, Connault E, Le Coz E, et al. Angiopoietin-like 4 prevents metastasis through inhibition of vascular permeability and tumor cell motility and invasiveness. Proc Natl Acad Sci U S A. 2006; 103: 18721–18726. https://doi.org/10.1073/pnas.0609025103 PMID: 17130448
Criscuoli ML, Nguyen M, Eliceiri BP. Tumor metastasis but not tumor growth is dependent on Src-mediated vascular permeability. Vascular. 2008; 105: 1508–1514. https://doi.org/10.1182/blood-2004-06-2246 PMID: 15486073
Satoh H, Moriguchi T, Taguchi K, Takai J, Maher JM, Suzuki T, et al. Nrf2-deficiency creates a responsive microenvironment for metastasis to the lung. Carcinogenesis. 2010; 31: 1833–1843. https://doi.org/10.1093/carcin/bgq105 PMID: 20513672
Zhong H, Gutkin DW, Han B, Ma Y, Keskinov AA, Shurin MR, et al. Origin and pharmacological modulation of tumor-associated regulatory dendritic cells. Int J Cancer. 2014; 134: 2633–2645. https://doi.org/10.1002/ijc.28590 PMID: 24443321
Pérez-Rial S, del Puerto-Nevado L, Terron-Exposito R, Giron-Martinez A, Gonzalez-Mangado N, Peces-Barba G. Role of Recently Migrated Monocytes in Cigarette Smoke-Induced Lung Inflammation in Different Strain of Mice. PLoS One. 2013; 8: 1–9. https://doi.org/10.1371/journal.pone.0072975 PMID: 24058452
Rosas M, Thomas B, Stacey M, Gordon S, Taylor PR. The myeloid 7/4-antigen defines recently generated inflammatory macrophages and is synonymous with Ly-6B. J Leukoc Biol. 2010; 88: 169–180. https://doi.org/10.1189/jlb.0809548 PMID: 20400676
Yoshimura T, Liu M, Chen X, Li L, Wang JM. Crosstalk between tumor cells and macrophages in stroma renders tumor cells as the primary source of MCP-1/CCL2 in Lewis lung carcinoma. Front Immunol. 2015; 6: 1–10. https://doi.org/10.3389/fimmu.2015.00332
Chen Y-R, Chou H-C, Yang C-H, Chen H-Y, Liu Y-W, Lin T-Y, et al. Deficiency in VHR/DUSP3, a suppressor of focal adhesion kinase, reveals its role in regulating cell adhesion and migration. Oncogene. 2017; https://doi.org/10.1038/onc.2017.255 PMID: 28759036
Sounni NE, Cimino J, Blacher S, Primac I, Truong A, Mazzucchelli G, et al. Blocking lipid synthesis overcomes tumor regrowth and metastasis after antiangiogenic therapy withdrawal. Cell Metab. Elsevier Inc.; 2014; 20: 280–294. https://doi.org/10.1016/j.cmet.2014.05.022 PMID: 25017943
Ebos JML, Lee CR, Cruz-Munoz W, Bjarnason GA, Christensen JG, Kerbel RS. Accelerated Metastasis after Short-Term Treatment with a Potent Inhibitor of Tumor Angiogenesis. Cancer Cell. Elsevier Ltd; 2009; 15: 232–239. https://doi.org/10.1016/j.ccr.2009.01.021 PMID: 19249681
Wong PP, Demircioglu F, Ghazaly E, Alrawashdeh W, Stratford MRL, Scudamore CL, et al. Dual-action combination therapy enhances angiogenesis while reducing tumor growth and spread. Cancer Cell. Elsevier Inc.; 2015; 27: 123–137. https://doi.org/10.1016/j.ccell.2014.10.015 PMID: 25584895
Donnem T, Hu J, Ferguson M, Adighibe O, Snell C, Harris AL, et al. Vessel co-option in primary human tumors and metastases: An obstacle to effective anti-angiogenic treatment? Cancer Med. 2013; 2: 427–436. https://doi.org/10.1002/cam4.105 PMID: 24156015
Frentzas S, Simoneau E, Bridgeman VL, Vermeulen PB, Foo S, Kostaras E, et al. Vessel co-option mediates resistance to anti-angiogenic therapy in liver metastases. Nat Med. 2016; 22: 1294–1302. https://doi.org/10.1038/nm.4197 PMID: 27748747
Kuczynski EA, Yin M, Bar-Zion A, Lee CR, Butz H, Man S, et al. Co-option of liver vessels and not sprouting angiogenesis drives acquired sorafenib resistance in hepatocellular carcinoma. J Natl Cancer Inst. 2016; 108: 1–13. https://doi.org/10.1093/jnci/djw030 PMID: 27059374