Atorvastatin (Lipitor) attenuates the effects of aspirin on pancreatic cancerogenesis and the chemotherapeutic efficacy of gemcitabine on pancreatic cancer by promoting M2 polarized tumor associated macrophages

Journal of Experimental and Clinical Cancer Research

Volumn 35, Issue 1, 2016, Pages

  Liu, Qiaofei ^a   Li, Yuan ^a   Niu, Zheyu ^a   Zong, Yi ^a   Wang, Mengyi ^a   Yao, Lutian ^a   Lu, Zhaohui ^a   Liao, Quan ^a   Zhao, Yupei ^a  

^a PEKING UNION MEDICAL COLLEGE HOSPITAL   (China)

Author keywords

Aspirin; Atorvastatin; Cancerogenesis; Chemotherapy; Gemcitabine; Myeloid derived suppressor cells; Pancreatic cancer; Tumor associated macrophages

Indexed keywords

ACETYLSALICYLIC ACID; ATORVASTATIN; CD45 ANTIGEN; DIMETHYLBENZ[A]ANTHRACENE; GEMCITABINE; 7,12 DIMETHYLBENZ[A]ANTHRACENE; ANTINEOPLASTIC ANTIMETABOLITE; DEOXYCYTIDINE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BIOACCUMULATION; CANCER CELL LINE; CANCER GROWTH; CANCER PREVENTION; CARCINOGENESIS; CONTROLLED STUDY; CYTOTOXIC T LYMPHOCYTE; DRUG ANTAGONISM; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENTIATION; FEMALE; HELPER CELL; IN VITRO STUDY; IN VIVO STUDY; INFLAMMATORY CELL; M2 POLARIZED TUMOR ASSOCIATED MACROPHAGE; MALE; MOLECULAR DYNAMICS; MOUSE; MYELOID DERIVED SUPPRESSOR CELL; NONHUMAN; PANC02 CELL LINE; PANCREAS CANCER; PANCREATIC CARCINOGENESIS; PRIORITY JOURNAL; SUPPRESSOR CELL; TUMOR ASSOCIATED LEUKOCYTE; TUMOR VOLUME; ANALOGS AND DERIVATIVES; ANIMAL; CELL LINE; CELL PROLIFERATION; CHEMICALLY INDUCED; CYTOLOGY; DRUG EFFECTS; DRUG SCREENING; GENE EXPRESSION REGULATION; MACROPHAGE; PANCREATIC NEOPLASMS; PATHOLOGY;

9,10-DIMETHYL-1,2-BENZANTHRACENE; ANIMALS; ANTIMETABOLITES, ANTINEOPLASTIC; ASPIRIN; ATORVASTATIN CALCIUM; CELL LINE; CELL PROLIFERATION; DEOXYCYTIDINE; DRUG SYNERGISM; GENE EXPRESSION REGULATION, NEOPLASTIC; MACROPHAGES; MALE; MICE; PANCREATIC NEOPLASMS; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84958256349     PISSN: None     EISSN: 17569966     Source Type: Journal    
DOI: 10.1186/s13046-016-0304-4     Document Type: Article

References (46)

1. DeSantis CE, Lin CC, Mariotto AB, Siegel RL, Stein KD, Kramer JL, et al. Cancer treatment and survivorship statistics, 2014. CA Cancer J Clin. 2014;64:252-71.
2. Hruban RH, Adsay NV, Albores-Saavedra J, Compton C, Garrett ES, Goodman SN, et al. Pancreatic intraepithelial neoplasia: a new nomenclature and classification system for pancreatic duct lesions. Am J Surg Pathol. 2001;25:579-86.
3. Sahoo RK, Kumar L. Albumin-bound paclitaxel plus gemcitabine in pancreatic cancer. N Engl J Med. 2014;370:478-9.
4. Erkan M, Hausmann S, Michalski CW, Fingerle AA, Dobritz M, Kleeff J, et al. The role of stroma in pancreatic cancer: diagnostic and therapeutic implications. Nat Rev Gastroenterol Hepatol. 2012;9:454-67.
5. Karakhanova S, Link J, Heinrich M, Shevchenko I, Yang Y, Hassenpflug M, et al. Characterization of myeloid leukocytes and soluble mediators in pancreatic cancer: importance of myeloid-derived suppressor cells. Oncoimmunology. 2015;4:e998519.
6. Gardian K, Janczewska S, Olszewski WL, Durlik M. Analysis of pancreatic cancer microenvironment: role of macrophage infiltrates and growth factors expression. J Cancer. 2012;3:285-91.
7. Kobayashi M, Shimodaira S, Nagai K, Ogasawara M, Takahashi H, Abe H, et al. Prognostic factors related to add-on dendritic cell vaccines on patients with inoperable pancreatic cancer receiving chemotherapy: a multicenter analysis. Cancer Immunol Immunother. 2014;63:797-806.
8. Carlson LM, Rasmuson A, Idborg H, Segerstrom L, Jakobsson PJ, Sveinbjornsson B, et al. Low-dose aspirin delays an inflammatory tumor progression in vivo in a transgenic mouse model of neuroblastoma. Carcinogenesis. 2013;34:1081-8.
9. Lee DK, Park EJ, Kim EK, Jin J, Kim JS, Shin IJ, et al. Atorvastatin and simvastatin, but not pravastatin, up-regulate LPS-induced MMP-9 expression in macrophages by regulating phosphorylation of ERK and CREB. Cell Physiol Biochem. 2012;30:499-511.
10. Shao Q, Shen LH, Hu LH, Pu J, Jing Q, He B. Atorvastatin suppresses inflammatory response induced by oxLDL through inhibition of ERK phosphorylation, IkappaBalpha degradation, and COX-2 expression in murine macrophages. J Cell Biochem. 2012;113:611-8.
11. Wender RC. Aspirin and NSAID chemoprevention, gene-environment interactions, and risk of colorectal cancer. JAMA. 2015;313:1111-2.
12. Bonovas S, Filioussi K, Sitaras NM. Statins are not associated with a reduced risk of pancreatic cancer at the population level, when taken at low doses for managing hypercholesterolemia: evidence from a meta-analysis of 12 studies. Am J Gastroenterol. 2008;103:2646-51.
13. Nielsen SF, Nordestgaard BG, Bojesen SE. Statin use and reduced cancer-related mortality. N Engl J Med. 2012;367:1792-802.
14. Liu Q, Zhang M, Jiang X, Zhang Z, Dai L, Min S, et al. miR-223 suppresses differentiation of tumor-induced CD11b(+) Gr1(+) myeloid-derived suppressor cells from bone marrow cells. Int J Cancer. 2011;129:2662-73.
15. Keklikoglou I, De Palma M. Cancer: Metastasis risk after anti-macrophage therapy. Nature. 2014;515:46-7.
16. Wynn TA, Chawla A, Pollard JW. Macrophage biology in development, homeostasis and disease. Nature. 2013;496:445-55.
17. Lavin Y, Winter D, Blecher-Gonen R, David E, Keren-Shaul H, Merad M, et al. Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment. Cell. 2014;159:1312-26.
18. Qian BZ, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell. 2010;141:39-51.
19. De Palma M, Lewis CE. Macrophage regulation of tumor responses to anticancer therapies. Cancer Cell. 2013;23:277-86.
20. Kimura K, Satoh K, Kanno A, Hamada S, Hirota M, Endoh M, et al. Activation of Notch signaling in tumorigenesis of experimental pancreatic cancer induced by dimethylbenzanthracene in mice. Cancer Sci. 2007;98:155-62.
21. Guo JC, Li J, Yang YC, Zhou L, Zhang TP, Zhao YP. Oligonucleotide microarray identifies genes differentially expressed during tumorigenesis of DMBA-induced pancreatic cancer in rats. PLoS One. 2013;8:e82910.
22. Markowitz J, Brooks TR, Duggan MC, Paul BK, Pan X, Wei L, et al. Patients with pancreatic adenocarcinoma exhibit elevated levels of myeloid-derived suppressor cells upon progression of disease. Cancer Immunol Immunother. 2015;64:149-59.
23. Khaled YS, Ammori BJ, Elkord E. Increased levels of granulocytic myeloid-derived suppressor cells in peripheral blood and tumour tissue of pancreatic cancer patients. J Immunol Res. 2014;2014:879897.
24. Zhao F, Obermann S, von Wasielewski R, Haile L, Manns MP, Korangy F, et al. Increase in frequency of myeloid-derived suppressor cells in mice with spontaneous pancreatic carcinoma. Immunology. 2009;128:141-9.
25. Panni RZ, Sanford DE, Belt BA, Mitchem JB, Worley LA, Goetz BD, et al. Tumor-induced STAT3 activation in monocytic myeloid-derived suppressor cells enhances stemness and mesenchymal properties in human pancreatic cancer. Cancer Immunol Immunother. 2014;63:513-28.
26. Cui TX, Kryczek I, Zhao L, Zhao E, Kuick R, Roh MH, et al. Myeloid-derived suppressor cells enhance stemness of cancer cells by inducing microRNA101 and suppressing the corepressor CtBP2. Immunity. 2013;39:611-21.
27. Kurahara H, Shinchi H, Mataki Y, Maemura K, Noma H, Kubo F, et al. Significance of M2-polarized tumor-associated macrophage in pancreatic cancer. J Surg Res. 2011;167:e211-219.
28. Ino Y, Yamazaki-Itoh R, Shimada K, Iwasaki M, Kosuge T, Kanai Y, et al. Immune cell infiltration as an indicator of the immune microenvironment of pancreatic cancer. Br J Cancer. 2013;108:914-23.
29. Liu CY, Xu JY, Shi XY, Huang W, Ruan TY, Xie P, et al. M2-polarized tumor-associated macrophages promoted epithelial-mesenchymal transition in pancreatic cancer cells, partially through TLR4/IL-10 signaling pathway. Lab Invest. 2013;93:844-54.
30. Angelova AL, Grekova SP, Heller A, Kuhlmann O, Soyka E, Giese T, et al. Complementary induction of immunogenic cell death by oncolytic parvovirus H-1PV and gemcitabine in pancreatic cancer. J Virol. 2014;88:5263-76.
31. Pei Q, Pan J, Ding X, Wang J, Zou X, Lv Y. Gemcitabine sensitizes pancreatic cancer cells to the CTLs antitumor response induced by BCG-stimulated dendritic cells via a Fas-dependent pathway. Pancreatology. 2015;15:233-9.
32. Le HK, Graham L, Cha E, Morales JK, Manjili MH, Bear HD. Gemcitabine directly inhibits myeloid derived suppressor cells in BALB/c mice bearing 4 T1 mammary carcinoma and augments expansion of T cells from tumor-bearing mice. Int Immunopharmacol. 2009;9:900-9.
33. Affara NI, Ruffell B, Medler TR, Gunderson AJ, Johansson M, Bornstein S, et al. B cells regulate macrophage phenotype and response to chemotherapy in squamous carcinomas. Cancer Cell. 2014;25:809-21.
34. Karagiannis P, Gilbert AE, Josephs DH, Ali N, Dodev T, Saul L, et al. IgG4 subclass antibodies impair antitumor immunity in melanoma. J Clin Invest. 2013;123:1457-74.
35. Nanda S. Cancer: CD40 agonists - a promising new treatment for pancreatic cancer? Nat Rev Gastroenterol Hepatol. 2011;8:300.
36. Hou YC, Chao YJ, Tung HL, Wang HC, Shan YS. Coexpression of CD44-positive/CD133-positive cancer stem cells and CD204-positive tumor-associated macrophages is a predictor of survival in pancreatic ductal adenocarcinoma. Cancer. 2014;120:2766-77.
37. Di Caro G, Cortese N, Castino GF, Grizzi F, Gavazzi F, Ridolfi C, et al. Dual prognostic significance of tumour-associated macrophages in human pancreatic adenocarcinoma treated or untreated with chemotherapy. Gut. 2015. [Epub ahead of print].
38. Sundararaj KP, Samuvel DJ, Li Y, Nareika A, Slate EH, Sanders JJ, et al. Simvastatin suppresses LPS-induced MMP-1 expression in U937 mononuclear cells by inhibiting protein isoprenylation-mediated ERK activation. J Leukoc Biol. 2008;84:1120-9.
39. Wang XQ, Luo NS, Salah ZQ, Lin YQ, Gu MN, Chen YX. Atorvastatin Attenuates TNF-alpha Production via Heme Oxygenase-1 Pathway in LPS-stimulated RAW264.7 Macrophages. Biomed Environ Sci. 2014;27:786-93.
40. Zhang O, Zhang J. Atorvastatin promotes human monocyte differentiation toward alternative M2 macrophages through p38 mitogen-activated protein kinase-dependent peroxisome proliferator-activated receptor gamma activation. Int Immunopharmacol. 2015;26:58-64.
41. Bradley MC, Hughes CM, Cantwell MM, Murray LJ. Statins and pancreatic cancer risk: a nested case-control study. Cancer Causes Control. 2010;21:2093-100.
42. Carey FJ, Little MW, Pugh TF, Ndokera R, Ing H, Clark A, et al. The differential effects of statins on the risk of developing pancreatic cancer: a case-control study in two centres in the United Kingdom. Dig Dis Sci. 2013;58:3308-12.
43. Vinogradova Y, Coupland C, Hippisley-Cox J. Exposure to statins and risk of common cancers: a series of nested case-control studies. BMC Cancer. 2011;11:409.
44. Friedman GD, Flick ED, Udaltsova N, Chan J, Quesenberry Jr CP, Habel LA. Screening statins for possible carcinogenic risk: up to 9 years of follow-up of 361,859 recipients. Pharmacoepidemiol Drug Saf. 2008;17:27-36.
45. Pastore A, Palleschi G, Fuschi A, Silvestri L, Al Salhi Y, Costantini E, et al. Can daily intake of aspirin and/or statins influence the behavior of non-muscle invasive bladder cancer? A retrospective study on a cohort of patients undergoing transurethral bladder resection. BMC Cancer. 2015;15:120.
46. Ravnskov U, McCully KS, Rosch PJ. The statin-low cholesterol-cancer conundrum. QJM. 2012;105:383-8.