Neutralizing murine TGFβR2 promotes a differentiated tumor cell phenotype and inhibits pancreatic cancer metastasis

Cancer Research

Volumn 74, Issue 18, 2014, Pages 4996-5007

  Ostapoff, Katherine T ^a,b   Cenik, Bercin Kutluk ^b   Wang, Miao ^b   Ye, Risheng ^a   Xu, Xiaohong ^c   Nugent, Desiree ^c   Hagopian, Moriah M ^a,b   Topalovski, Mary ^b   Rivera, Lee B ^b   Carroll, Kyla D ^c   Brekken, Rolf A ^a,b  

^a UNIVERSITY OF TEXAS AT DALLAS   (United States)

^b UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^c ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC ANTIMETABOLITE; DEOXYCYTIDINE; GEMCITABINE; MONOCLONAL ANTIBODY; TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA RECEPTOR;

3T3 CELL LINE; ANALOGS AND DERIVATIVES; ANIMAL; ANTAGONISTS AND INHIBITORS; C57BL MOUSE; CELL DIFFERENTIATION; DRUG EFFECTS; DRUG SCREENING; HUMAN; METABOLISM; METASTASIS; MOUSE; PANCREATIC NEOPLASMS; PATHOLOGY; RANDOMIZATION; SIGNAL TRANSDUCTION; TUMOR CELL LINE;

ANIMALS; ANTIBODIES, MONOCLONAL; ANTIMETABOLITES, ANTINEOPLASTIC; CELL DIFFERENTIATION; CELL LINE, TUMOR; DEOXYCYTIDINE; HUMANS; MICE; MICE, INBRED C57BL; NEOPLASM METASTASIS; NIH 3T3 CELLS; PANCREATIC NEOPLASMS; RANDOM ALLOCATION; RECEPTORS, TRANSFORMING GROWTH FACTOR BETA; SIGNAL TRANSDUCTION; TRANSFORMING GROWTH FACTOR BETA; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84907494552     PISSN: 00085472     EISSN: 15387445     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-13-1807     Document Type: Article

References (43)

1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin 2012;62:10-29.
2. Hanahan D, Coussens LM. Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell 2012;21:309-22.
3. Corcoran RB, Contino G, Deshpande V, Tzatsos A, Conrad C, Benes CH, et al. STAT3 plays a critical role in KRAS-induced pancreatic tumorigenesis. Cancer Res 2011;71:5020-9.
4. Yang L, Pang Y, Moses HL. TGF-beta and immune cells: an important regulatory axis in the tumor microenvironment and progression. Trends Immunol 2010;31:220-7.
5. Jones S, Zhang X, Parsons DW, Lin JC, Leary RJ, Angenendt P, et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 2008;321:1801-6.
6. Izeradjene K, Combs C, Best M, Gopinathan A, Wagner A, Grady WM, et al. Kras (G12D) and Smad4/Dpc4 haploinsufficiency cooperate to induce mucinous cystic neoplasms and invasive adenocarcinoma of the pancreas. Cancer Cell 2007;11:229-43.
7. Ijichi H, Chytil A, Gorska AE, Aakre ME, Fujitani Y, Fujitani S, et al. Aggressive pancreatic ductal adenocarcinoma in mice caused by pancreas-specific blockade of transforming growth factor-beta signaling in cooperation with active Kras expression. Genes Dev 2006;20:3147-60.
8. Bardeesy N, Cheng KH, Berger JH, Chu GC, Pahler J, Olson P, et al. Smad4 is dispensable for normal pancreas development yet critical in progression and tumor biology of pancreas cancer. Genes Dev 2006;20:3130-46.
9. Nolan-Stevaux O, Lau J, Truitt ML, Chu GC, Hebrok M, Fernandez-Zapico ME, et al. GLI1 is regulated through Smoothened-independent mechanisms in neoplastic pancreatic ducts and mediates PDAC cell survival and transformation. Genes Dev 2009;23:24-36.
10. Friess H, Yamanaka Y, Buchler M, Ebert M, Beger HG, Gold LI, et al. Enhanced expression of transforming growth factor beta isoforms in pancreatic cancer correlates with decreased survival. Gastroenterology 1993;105:1846-56.
11. Zhao S, Venkatasubbarao K, Lazor JW, Sperry J, Jin C, Cao L, et al. Inhibition of STAT3 Tyr705 phosphorylation by Smad4 suppresses transforming growth factor beta-mediated invasion and metastasis in pancreatic cancer cells. Cancer Res 2008;68:4221-8.
12. Melisi D, Ishiyama S, Sclabas GM, Fleming JB, Xia Q, Tortora G, et al. LY2109761, a novel transforming growth factor beta receptor type I and type II dual inhibitor, as a therapeutic approach to suppressing pancreatic cancer metastasis. Mol Cancer Ther 2008;7:829-40.
13. Truty MJ, Urrutia R. Basics of TGF-beta and pancreatic cancer. Pancreatology 2007;7:423-35.
14. Lohr M, Schmidt C, Ringel J, Kluth M, Muller P, Nizze H, et al. Transforming growth factor-beta1 induces desmoplasia in an experimental model of human pancreatic carcinoma. Cancer Res 2001;61:550-5.
15. Achyut BR, Yang L. Transforming growth factor-beta in the gastrointestinal and hepatic tumor microenvironment. Gastroenterology 2011;141:1167-78.
16. Zhong Z, Carroll KD, Policarpio D, Osborn C, Gregory M, Bassi R, et al. Anti-transforming growth factor beta receptor II antibody has therapeutic efficacy against primary tumor growth and metastasis through multieffects on cancer, stroma, and immune cells. Clin Cancer Res 2010;16:1191-205.
17. Dineen SP, Roland CL, Greer R, Carbon JG, Toombs JE, Gupta P, et al. Smac mimetic increases chemotherapy response and improves survival in mice with pancreatic cancer. Cancer Res 2010;70:2852-61.
18. Aguirre AJ, Bardeesy N, Sinha M, Lopez L, Tuveson DA, Horner J, et al. Activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinoma. Genes Dev 2003;17:3112-26.
19. Krantz SB, Shields MA, Dangi-Garimella S, Cheon EC, Barron MR, Hwang RF, et al. MT1-MMP cooperates with Kras (G12D) to promote pancreatic fibrosis through increased TGF-beta signaling. Mol Cancer Res 2011;9:1294-304.
20. Orimo A, Gupta PB, Sgroi DC, Arenzana-Seisdedos F, Delaunay T, Naeem R, et al. Stromal fibroblasts present in invasive human breast carcinomaspromote tumor growth and angiogenesis throughelevated SDF-1/CXCL12 secretion. Cell 2005;121:335-48.
21. Taipale J, Saharinen J, Keski-Oja J. Extracellular matrix-associated transforming growth factor-beta: role in cancer cell growth and invasion. Adv Cancer Res 1998;75:87-134.
22. Shields MA, Dangi-Garimella S, Redig AJ, Munshi HG. Biochemical role of the collagen-rich tumour microenvironment in pancreatic cancer progression. Biochem J 2012;441:541-52.
23. Dangi-Garimella S, Krantz SB, Barron MR, Shields MA, Heiferman MJ, Grippo PJ, et al. Three-dimensional collagen I promotes gemcitabine resistance in pancreatic cancer through MT1-MMP-mediated expression of HMGA2. Cancer Res 2011;71:1019-28.
24. Olive KP, Jacobetz MA, Davidson CJ, Gopinathan A, McIntyre D, Honess D, et al. Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science 2009;324:1457-61.
25. Provenzano PP, Cuevas C, Chang AE, Goel VK, Von Hoff DD, Hingorani SR. Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma. Cancer Cell 2012;21:418-29.
26. Qian BZ, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell 2010;141:39-51.
27. Pinson DM, Le Claire RD, Lorsbach RB, Parmely MJ, Russell SW. Regulation by transforming growth factor-beta 1 of expression and function of the receptor for IFN-gamma on mouse macrophages. J Immunol 1992;149:2028-34.
28. Biswas SK, Gangi L, Paul S, Schioppa T, Saccani A, Sironi M, et al. A distinct and unique transcriptional program expressed by tumorassociated macrophages (defective NF-kappaB and enhanced IRF-3/STAT1 activation). Blood 2006;107:2112-22.
29. Condeelis J, Pollard JW. Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell 2006;124:263-6.
30. Ellenrieder V, Hendler SF, Boeck W, Seufferlein T, Menke A, Ruhland C, et al. Transforming growth factor beta1 treatment leadsto an epithelialmesenchymal transdifferentiation of pancreatic cancer cells requiring extracellular signal-regulated kinase 2 activation. Cancer Res 2001;61:4222-8.
31. Tsuji T, Ibaragi S, Hu GF. Epithelial-mesenchymal transition and cell cooperativity in metastasis. Cancer Res 2009;69:7135-9.
32. Chen L, Chan TH, Yuan YF, Hu L, Huang J, Ma S, et al. CHD1L promotes hepatocellular carcinoma progression and metastasis in mice and is associated with these processes in human patients. J Clin Invest 2010;120:1178-91.
33. Teraoka H, Sawada T, Nishihara T, Yashiro M, Ohira M, Ishikawa T, et al. Enhanced VEGF production and decreased immunogenicity induced by TGF-beta 1 promote liver metastasis of pancreatic cancer. Br J Cancer 2001;85:612-7.
34. Teraoka H, Sawada T, Yamashita Y, Nakata B, Ohira M, Ishikawa T, et al. TGF-beta1 promotes liver metastasis of pancreatic cancer by modulating the capacity of cellular invasion. Int J Oncol 2001;19:709-15.
35. Arnold SA, Rivera LB, Carbon JG, Toombs JE, Chang CL, Bradshaw AD, et al. Losartan slows pancreatic tumor progression and extends survival of SPARC-Null mice by abrogating aberrant TGFbeta activation. PLoS ONE 2012;7:e31384.
36. Rhim AD, Mirek ET, Aiello NM, Maitra A, Bailey JM, McAllister F, et al. EMT and dissemination precede pancreatic tumor formation. Cell 2012;148:349-61.
37. Arumugam T, Ramachandran V, Fournier KF, Wang H, Marquis L, Abbruzzese JL, et al. Epithelial to mesenchymal transition contributes to drug resistance in pancreatic cancer. Cancer Res 2009;69:5820-8.
38. Ding Q, Yoshimitsu M, Kuwahata T, Maeda K, Hayashi T, Obara T, et al. Establishment of a highly migratory subclone reveals that CD133 contributes to migration and invasion through epithelial-mesenchymal transition in pancreatic cancer. Hum Cell 2012;25:1-8.
39. Kim MP, Evans DB, Wang H, Abbruzzese JL, Fleming JB, Gallick GE. Generation of orthotopic and heterotopic human pancreatic cancer xenografts in immunodeficient mice. Nat Protoc 2009;4:1670-80.
40. Medicherla S, Li L, Ma JY, Kapoun AM, Gaspar NJ, Liu YW, et al. Antitumor activity of TGF-beta inhibitor is dependent on the microenvironment. Anticancer Res 2007;27:4149-57.
41. Hezel AF, Deshpande V, Zimmerman SM, Contino G, Alagesan B, O'Dell MR, et al. TGF-beta and alphavbeta6 integrin act in a common pathway to suppress pancreatic cancer progression. Cancer Res 2012;72:4840-5.
42. Munger JS, Huang X, Kawakatsu H, Griffiths MJ, Dalton SL, Wu J, et al. The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis. Cell 1999;96:319-28.
43. Garber K. Stromal depletion goes on trial in pancreatic cancer. J Natl Cancer Inst 2010;102:448-50.