MerTK inhibition in tumor leukocytes decreases tumor growth and metastasis

Journal of Clinical Investigation

Volumn 123, Issue 8, 2013, Pages 3231-3242

  Cook, Rebecca S ^a,b   Jacobsen, Kristen M ^c,d   Wofford, Anne M ^e   DeRyckere, Deborah ^d   Stanford, Jamie ^a   Prieto, Anne L ^f   Redente, Elizabeth ^g   Sandahl, Melissa ^h   Hunter, Debra M ^h   Strunk, Karen E ^h   Graham, Douglas K ^c,d   Earp Iii, H Shelton ^h  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b VANDERBILT INGRAM CANCER CENTER   (United States)

^c Department of Integrated Immunology ^*  (United States)

^d Children's Hospital Colorado   (United States)

^e WAKE FOREST SCHOOL OF MEDICINE   (United States)

^f INDIANA UNIVERSITY   (United States)

^g DEPARTMENT OF MEDICINE   (United States)

^h UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GROWTH ARREST SPECIFIC PROTEIN 6; INTERLEUKIN 10; MERTK PROTEIN; PROTEIN TYROSINE KINASE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BONE MARROW TRANSPLANTATION; BREAST CANCER; CD8+ T LYMPHOCYTE; CELL PROLIFERATION; COLON CANCER; CONTROLLED STUDY; CYTOKINE PRODUCTION; LEUKOCYTE; MELANOMA; METASTASIS; MOUSE; NONHUMAN; PRIORITY JOURNAL; TUMOR GROWTH; WILD TYPE; WOUND HEALING;

ANIMALS; CD8-POSITIVE T-LYMPHOCYTES; COLONIC NEOPLASMS; CYTOKINES; DISEASE RESISTANCE; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; LEUKOCYTES; MALE; MAMMARY NEOPLASMS, EXPERIMENTAL; MELANOMA, EXPERIMENTAL; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; NEOPLASM TRANSPLANTATION; PROTO-ONCOGENE PROTEINS; RECEPTOR PROTEIN-TYROSINE KINASES; TRANSCRIPTOME; TUMOR BURDEN; TUMOR MICROENVIRONMENT;

EID: 84881260689     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI67655     Document Type: Article

References (57)

1. Linger RM, Keating AK, Earp HS, Graham DK. Taking aim at Mer and Axl receptor tyrosine kinases as novel therapeutic targets in solid tumors. Expert Opin Ther Targets. 2010;14(10):1073-1090.
2. Linger RM, Keating AK, Earp HS, Graham DK. TAM receptor tyrosine kinases: biologic functions, signaling, and potential therapeutic targeting in human cancer. Adv Cancer Res. 2008;100:35-83.
3. Lemke G, Rothlin CV. Immunobiology of the TAM receptors. Nat Rev Immunol. 2008;8(5):327-336.
4. Rothlin CV, Lemke G. TAM receptor signaling and autoimmune disease. Curr Opin Immunol. 2010; 22(6):740-746.
5. Brown J, Krodel M, Pazos M, Lai C, Prieto A. Crossphosphorylation, signaling and proliferative functions of the Tyro-3 and Axl receptors in Rat2 cells. PLoS One. 2012;7(5):e36800.
6. Graham DK, Dawson TL, Mullaney DL, Snodgrass HR, Earp HS. Cloning and mRNA expression analysis of a novel human protooncogene, c-mer. Cell Growth Differ. 1994;5(6):647-657.
7. Nagata K, et al. Identification of the product of growth arrest-specific gene 6 as a common ligand for Axl, Sky, and Mer receptor tyrosine kinases. J Biol Chem. 1996;271(47):30022-30027.
8. Varnum B, et al. Axl receptor tyrosine kinase stimulated by the vitamin K-dependent protein encoded by growth-arrest-specific gene 6. Nature. 1995;373(6515):623-626.
9. Hafizi S, Dahlback B. Gas6 and protein S. Vitamin K-dependent ligands for the Axl receptor tyrosine kinase subfamily. FEBS J. 2006;273(23):5231-5244.
10. Stitt TN, et al. The anticoagulation factor protein S and its relative, Gas6, are ligands for the Tyro 3/ Axl family of receptor tyrosine kinases. Cell. 1995; 80(4):661-670.
11. Caberoy NB, Zhou Y, Li W. Tubby and tubby-like protein 1 are new MerTK ligands for phagocytosis. EMBO J. 2010;29(23):3898-3910.
12. Caberoy NB, Alvarado G, Bigcas J, Li W. Galectin-3 is a new MerTK-specific eat-me signal. J Cell Physiology. 2011;227(2):401-407.
13. Wang Y, et al. Mer receptor tyrosine kinase promotes invasion and survival in glioblastoma multiforme. Oncogene. 2013;32(7):872-882.
14. Png KJ, Halberg N, Yoshida M, Tavazoie SF. A microRNA regulon that mediates endothelial recruitment and metastasis by cancer cells. Nature. 2012; 481(7380):190-194.
15. Jansen FH, et al. Profiling of antibody production against xenograft-released proteins by protein microarrays discovers prostate cancer markers. J Proteome Res. 2012;11(2):728-735.
16. Tworkoski K, et al. Phosphoproteomic screen identifies potential therapeutic targets in melanoma. Mol Cancer Res. 2011;9(6):801-812.
17. Keating AK, et al. Inhibition of Mer and Axl receptor tyrosine kinases in astrocytoma cells leads to increased apoptosis and improved chemosensitivity. Mol Cancer Ther. 2010;9(5):1298-1307.
18. Graham DK, et al. Ectopic expression of the protooncogene Mer in pediatric T-cell acute lymphoblastic leukemia. Clin Cancer Res. 2006;12(9):2662-2669.
19. Keating AK, et al. Lymphoblastic leukemia/lymphoma in mice overexpressing the Mer (MerTK) receptor tyrosine kinase. Oncogene. 2006;25(45):6092-6100.
20. Behrens EM, Gadue P, Gong SY, Garrett S, Stein PL, Cohen PL. The mer receptor tyrosine kinase: expression and function suggest a role in innate immunity. Eur J Immunol. 2003;33(8):2160-2167.
21. Rothlin CV, Ghosh S, Zuniga EI, Oldstone MB, Lemke G. TAM receptors are pleiotropic inhibitors of the innate immune response. Cell. 2007; 131(6):1124-1136.
22. Fadok VA, Voelker DR, Campbell PA, Cohen JJ, Bratton DL, Henson PM. Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. J Immunol. 1992;148(7):2207- 2216.
23. Scott RS, et al. Phagocytosis and clearance of apoptotic cells is mediated by MER. Nature. 2001; 411(6834):207-211.
24. Seitz HM, Camenisch TD, Lemke G, Earp HS, Matsushima GK. Macrophages and dendritic cells use different Axl/Mertk/Tyro3 receptors in clearance of apoptotic cells. J Immunol. 2007;178(9):5635-5642.
25. Tibrewal N, et al. Autophosphorylation docking site Tyr-867 in Mer receptor tyrosine kinase allows for dissociation of multiple signaling pathways for phagocytosis of apoptotic cells and down-modulation of lipopolysaccharide- inducible NF-kappaB transcriptional activation. J Biol Chem. 2008;283(6):3618-3627.
26. Filardy AA, et al. Proinflammatory clearance of apoptotic neutrophils induces an IL-12(low) IL-10(high) regulatory phenotype in macrophages. J Immunol. 2010;185(4):2044-2050.
27. Gal A, et al. Mutations in MERTK, the human orthologue of the RCS rat retinal dystrophy gene, cause retinitis pigmentosa. Nat Genet. 2000;26(3):270-271.
28. Sandahl M, Hunter DM, Strunk KE, Earp HS, Cook RS. Epithelial cell-directed efferocytosis in the post-partum mammary gland is necessary for tissue homeostasis and future lactation. BMC Dev Biol. 2010;10:122.
29. Cohen PL, et al. Delayed apoptotic cell clearance and lupus-like autoimmunity in mice lacking the c-mer membrane tyrosine kinase. J Exp Med. 2002; 196(1):135-140.
30. Camenisch TD, Koller BH, Earp HS, Matsushima GK. A novel receptor tyrosine kinase, Mer, inhibits TNFalpha production and lipopolysaccharide- induced endotoxic shock. J Immunol. 1999;162(6):3498-3503.
31. Shao WH, Eisenberg RA, Cohen PL. The Mer receptor tyrosine kinase is required for the loss of B cell tolerance in the chronic graft-versus-host disease model of systemic lupus erythematosus. J Immunol. 2008;180(11):7728- 7735.
32. Shao WH, et al. Disrupted Mer receptor tyrosine kinase expression leads to enhanced MZ B-cell responses. J Autoimmun. 2010;35(4):368-374.
33. Lu Q, et al. Tyro-3 family receptors are essential regulators of mammalian spermatogenesis. Nature. 1999;398(6729):723-728.
34. Pollard JW. Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer. 2004;4(1):71-78.
35. Pollard JW. Trophic macrophages in development and disease. Nat Rev Immunol. 2009;9(4):259-270.
36. Ruffell B, Affara NI, Coussens LM. Differential macrophage programming in the tumor microenvironment. Trends Immunol. 2012;33(3):119-126.
37. Lin EY, Nguyen AV, Russell RG, Pollard JW. Colony- stimulating factor 1 promotes progression of mammary tumors to malignancy. J Exp Med. 2001; 193(6):727-740.
38. Denardo DG, et al. Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy. Cancer Discov. 2011; 1(1):54-67.
39. Wyckoff J, et al. A paracrine loop between tumor cells and macrophages is required for tumor cell migration in mammary tumors. Cancer Res. 2004; 64(19):7022-7029.
40. Qian B, et al. A distinct macrophage population mediates metastatic breast cancer cell extravasation, establishment and growth. PLoS One. 2009;4(8):e6562.
41. Qian BZ, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell. 2010; 141(1):39-51.
42. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010;140(6):883-899.
43. Trinchieri G. Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol. 2003;3(2):133-146.
44. Guy CT, Cardiff RD, Muller WJ. Induction of mammary tumors by expression of polyomavirus middle T oncogene: a transgenic mouse model for metastatic disease. Mol Cell Biol. 1992;12(3):954-961.
45. Kidd S, et al. Origins of the tumor microenvironment: quantitative assessment of adipose-derived and bone marrow-derived stroma. PLoS One. 2012; 7(2):e30563.
46. Loges S, et al. Malignant cells fuel tumor growth by educating infiltrating leukocytes to produce the mitogen Gas6. Blood. 2010;115(11):2264- 2273.
47. Friggeri A, Yang Y, Banerjee S, Park YJ, Liu G, Abraham E. HMGB1 inhibits macrophage activity in efferocytosis through binding to the alphavbeta3- integrin. Am J Physiol Cell Physiol. 2010; 299(6):C1267-C1276.
48. Nowicki A, et al. Impaired tumor growth in colony- stimulating factor 1 (CSF-1)-deficient, macrophage- deficient op/op mouse: evidence for a role of CSF-1-dependent macrophages in formation of tumor stroma. Int J Cancer. 1996;65(1):112-119.
49. O'Brien J, et al. Alternatively activated macrophages and collagen remodeling characterize the postpartum involuting mammary gland across species. Am J Pathol. 2010;176(3):1241-1255.
50. Lemke G, Lu Q. Macrophage regulation by Tyro 3 family receptors. Curr Opin Immunol. 2003; 15(1):31-36.
51. Lu Q, Lemke G. Homeostatic regulation of the immune system by receptor tyrosine kinases of the Tyro 3 family. Science. 2001;293(5528):306-311.
52. Kristensen VN, et al. Integrated molecular profiles of invasive breast tumors and ductal carcinoma in situ (DCIS) reveal differential vascular and interleukin signaling. Proc Natl Acad Sci U S A. 2012; 109(8):2802-2807.
53. Teschendorff AE, et al. Improved prognostic classification of breast cancer defined by antagonistic activation patterns of immune response pathway modules. BMC Cancer. 2010;10:604.
54. Coussens L, Zitvogel L, Palucka K. Neutralizing tumor-promoting chronic inflammation: a magic bullet? Science 2013;339(6117):286-291.
55. Cook RS, et al. ErbB3 ablation impairs PI3K/ Akt-dependent mammary tumorigenesis. Cancer Res. 2011;71(11):3941-3951.
56. Balko JM, et al. The receptor tyrosine kinase ErbB3 maintains the balance between luminal and basal breast epithelium. Proc Natl Acad Sci U S A. 2012;109(1):221-226.
57. Redente EF, Orlicky DJ, Bouchard RJ, Malkinson AM. Tumor signaling to the bone marrow changes the phenotype of monocytes and pulmonary macrophages during urethane-induced primary lung tumorigenesis in A/J mice. Am J Pathol. 2007; 170(2):693-708.