Skip to main content
Top
Published in: Tumor Biology 12/2015

Open Access 01-12-2015 | Review

Functional significance of macrophages in pancreatic cancer biology

Authors: Hai Hu, Feng Jiao, Ting Han, Li-Wei Wang

Published in: Tumor Biology | Issue 12/2015

Login to get access

Abstract

Pancreatic ductal adenocarcinoma (PDA) is a lethal disease that is usually diagnosed at late stage with few effective therapies. Despite the rapid progress on the genomics and proteomics of the neoplastic cells, therapies that targeted the pancreatic cancer cells proved to be inefficient, which promoted the researchers to turn their attentions to the microenvironment. Currently, various studies had proposed the microenvironment to be a contributing factor for PDA and pervasive researches showed that macrophages within the malignancy correlate with the malignant phenotype of the disease and were reported to a new therapeutic target. Generally, the pro-tumoral effects of macrophages can be summarized as angiogenesis promotion, immunosuppression, matrix remodeling and so on. Hence, a comprehensive understanding of the biologic behaviors of macrophages and their critical role in PDA development may provide new directions for the managements of the lethal disease. In this review, we will summarize the recent advancements on macrophages as pivotal players in PDA biology and the current knowledge about anti-macrophages as a novel strategy against cancer, with the expectation that more efficient therapies will be developed in the near future.
Literature
1.
4.
go back to reference Hr B, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997;15:2403–13.CrossRef Hr B, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997;15:2403–13.CrossRef
5.
go back to reference Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007;357:2666–76.CrossRefPubMed Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007;357:2666–76.CrossRefPubMed
6.
go back to reference Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350:2335–42.CrossRefPubMed Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350:2335–42.CrossRefPubMed
7.
go back to reference Neesse A, Michl P, Frese KK, Feig C, Cook N, Jacobetz MA, et al. Stromal biology and therapy in pancreatic cancer. Gut. 2011;60:861–8.CrossRefPubMed Neesse A, Michl P, Frese KK, Feig C, Cook N, Jacobetz MA, et al. Stromal biology and therapy in pancreatic cancer. Gut. 2011;60:861–8.CrossRefPubMed
8.
go back to reference van Furth R. Origin and turnover of monocytes and macrophages; cell kinetics of the inflammatory reaction. Berlin Heidelberg: Springer; 1989. pp. 125–50. van Furth R. Origin and turnover of monocytes and macrophages; cell kinetics of the inflammatory reaction. Berlin Heidelberg: Springer; 1989. pp. 125–50.
9.
go back to reference Ries CH, Cannarile MA, Hoves S, Benz J, Wartha K, Runza V, et al. Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy. Cancer Cell. 2014;25:846–59.CrossRefPubMed Ries CH, Cannarile MA, Hoves S, Benz J, Wartha K, Runza V, et al. Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy. Cancer Cell. 2014;25:846–59.CrossRefPubMed
10.
go back to reference Sanford DE, Belt BA, Panni RZ, Mayer A, Deshpande AD, Carpenter D, et al. Inflammatory monocyte mobilization decreases patient survival in pancreatic cancer: a role for targeting the CCL2/CCR2 axis. Clin Cancer Res. 2013;19:3404–15.CrossRefPubMedPubMedCentral Sanford DE, Belt BA, Panni RZ, Mayer A, Deshpande AD, Carpenter D, et al. Inflammatory monocyte mobilization decreases patient survival in pancreatic cancer: a role for targeting the CCL2/CCR2 axis. Clin Cancer Res. 2013;19:3404–15.CrossRefPubMedPubMedCentral
11.
go back to reference Curtis VF, Wang H, Yang P, McLendon RE, Li X, Zhou QY, et al. A PK2/Bv8/PROK2 antagonist suppresses tumorigenic processes by inhibiting angiogenesis in glioma and blocking myeloid cell infiltration in pancreatic cancer. PLoS One. 2013;8:e54916.CrossRefPubMedPubMedCentral Curtis VF, Wang H, Yang P, McLendon RE, Li X, Zhou QY, et al. A PK2/Bv8/PROK2 antagonist suppresses tumorigenic processes by inhibiting angiogenesis in glioma and blocking myeloid cell infiltration in pancreatic cancer. PLoS One. 2013;8:e54916.CrossRefPubMedPubMedCentral
12.
go back to reference Murdoch C, Giannoudis A, Lewis CE. Mechanisms regulating the recruitment of macrophages into hypoxic areas of tumors and other ischemic tissues. Blood. 2004;104:2224–34.CrossRefPubMed Murdoch C, Giannoudis A, Lewis CE. Mechanisms regulating the recruitment of macrophages into hypoxic areas of tumors and other ischemic tissues. Blood. 2004;104:2224–34.CrossRefPubMed
13.
go back to reference Biswas SK, Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol. 2010;11:889–96.CrossRefPubMed Biswas SK, Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol. 2010;11:889–96.CrossRefPubMed
15.
go back to reference 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:e211–9.CrossRefPubMed 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:e211–9.CrossRefPubMed
16.
go back to reference Yoshikawa K, Mitsunaga S, Kinoshita T, Konishi M, Takahashi S, Gotohda N, Kato Y, Aizawa M, Ochiai A. Impact of tumor‐associated macrophages on invasive ductal carcinoma of the pancreas head. Cancer science 2012;103(11):2012–20. Yoshikawa K, Mitsunaga S, Kinoshita T, Konishi M, Takahashi S, Gotohda N, Kato Y, Aizawa M, Ochiai A. Impact of tumor‐associated macrophages on invasive ductal carcinoma of the pancreas head. Cancer science 2012;103(11):2012–20.
17.
go back to reference An T, Sood U, Pietruk T, Cummings G, Hashimoto K, Crissman J. In situ quantitation of inflammatory mononuclear cells in ductal infiltrating breast carcinoma. Relation to prognostic parameters. Am J Pathol. 1987;128:52.PubMedPubMedCentral An T, Sood U, Pietruk T, Cummings G, Hashimoto K, Crissman J. In situ quantitation of inflammatory mononuclear cells in ductal infiltrating breast carcinoma. Relation to prognostic parameters. Am J Pathol. 1987;128:52.PubMedPubMedCentral
18.
go back to reference Hiraoka K, Zenmyo M, Watari K, Iguchi H, Fotovati A, Kimura YN, et al. Inhibition of bone and muscle metastases of lung cancer cells by a decrease in the number of monocytes/macrophages. Cancer Sci. 2008;99:1595–602.CrossRefPubMed Hiraoka K, Zenmyo M, Watari K, Iguchi H, Fotovati A, Kimura YN, et al. Inhibition of bone and muscle metastases of lung cancer cells by a decrease in the number of monocytes/macrophages. Cancer Sci. 2008;99:1595–602.CrossRefPubMed
19.
go back to reference Lin EY, Li J-F, Gnatovskiy L, Deng Y, Zhu L, Grzesik DA, et al. Macrophages regulate the angiogenic switch in a mouse model of breast cancer. Cancer Res. 2006;66:11238–46.CrossRefPubMed Lin EY, Li J-F, Gnatovskiy L, Deng Y, Zhu L, Grzesik DA, et al. Macrophages regulate the angiogenic switch in a mouse model of breast cancer. Cancer Res. 2006;66:11238–46.CrossRefPubMed
20.
go back to reference Zeisberger S, Odermatt B, Marty C, Zehnder-Fjällman A, Ballmer-Hofer K, Schwendener R. Clodronate-liposome-mediated depletion of tumour-associated macrophages: a new and highly effective antiangiogenic therapy approach. Br J Cancer. 2006;95:272–81.CrossRefPubMedPubMedCentral Zeisberger S, Odermatt B, Marty C, Zehnder-Fjällman A, Ballmer-Hofer K, Schwendener R. Clodronate-liposome-mediated depletion of tumour-associated macrophages: a new and highly effective antiangiogenic therapy approach. Br J Cancer. 2006;95:272–81.CrossRefPubMedPubMedCentral
21.
go back to reference Condeelis J, Pollard JW. Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell. 2006;124:263–6.CrossRefPubMed Condeelis J, Pollard JW. Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell. 2006;124:263–6.CrossRefPubMed
22.
go back to reference Casazza A, Laoui D, Wenes M, Rizzolio S, Bassani N, Mambretti M, et al. Impeding macrophage entry into hypoxic tumor areas by Sema3A/Nrp1 signaling blockade inhibits angiogenesis and restores antitumor immunity. Cancer Cell. 2013;24:695–709.CrossRefPubMed Casazza A, Laoui D, Wenes M, Rizzolio S, Bassani N, Mambretti M, et al. Impeding macrophage entry into hypoxic tumor areas by Sema3A/Nrp1 signaling blockade inhibits angiogenesis and restores antitumor immunity. Cancer Cell. 2013;24:695–709.CrossRefPubMed
23.
go back to reference Greten FR, Eckmann L, Greten TF, Park JM, Li Z-W, Egan LJ, et al. IKKβ links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell. 2004;118:285–96.CrossRefPubMed Greten FR, Eckmann L, Greten TF, Park JM, Li Z-W, Egan LJ, et al. IKKβ links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell. 2004;118:285–96.CrossRefPubMed
24.
go back to reference Qian B, Deng Y, Im JH, Muschel RJ, Zou Y, Li J, et al. A distinct macrophage population mediates metastatic breast cancer cell extravasation, establishment and growth. PLoS One. 2009;4:e6562.CrossRefPubMedPubMedCentral Qian B, Deng Y, Im JH, Muschel RJ, Zou Y, Li J, et al. A distinct macrophage population mediates metastatic breast cancer cell extravasation, establishment and growth. PLoS One. 2009;4:e6562.CrossRefPubMedPubMedCentral
26.
go back to reference Xue J, Schmidt SV, Sander J, Draffehn A, Krebs W, Quester I, et al. Transcriptome-based network analysis reveals a spectrum model of human macrophage activation. Immunity. 2014;40:274–88.CrossRefPubMedPubMedCentral Xue J, Schmidt SV, Sander J, Draffehn A, Krebs W, Quester I, et al. Transcriptome-based network analysis reveals a spectrum model of human macrophage activation. Immunity. 2014;40:274–88.CrossRefPubMedPubMedCentral
27.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
28.
go back to reference Apte MV, Wilson JS, Lugea A, Pandol SJ. A starring role for stellate cells in the pancreatic cancer microenvironment. Gastroenterology. 2013;144:1210–9.CrossRefPubMedPubMedCentral Apte MV, Wilson JS, Lugea A, Pandol SJ. A starring role for stellate cells in the pancreatic cancer microenvironment. Gastroenterology. 2013;144:1210–9.CrossRefPubMedPubMedCentral
29.
go back to reference Apte MV, Park S, Phillips PA, Santucci N, Goldstein D, Kumar RK, et al. Desmoplastic reaction in pancreatic cancer: role of pancreatic stellate cells. Pancreas. 2004;29:179–87.CrossRefPubMed Apte MV, Park S, Phillips PA, Santucci N, Goldstein D, Kumar RK, et al. Desmoplastic reaction in pancreatic cancer: role of pancreatic stellate cells. Pancreas. 2004;29:179–87.CrossRefPubMed
30.
go back to reference Infante JR, Matsubayashi H, Sato N, Tonascia J, Klein AP, Riall TA, et al. Peritumoral fibroblast SPARC expression and patient outcome with resectable pancreatic adenocarcinoma. J Clin Oncol. 2007;25:319–25.CrossRefPubMed Infante JR, Matsubayashi H, Sato N, Tonascia J, Klein AP, Riall TA, et al. Peritumoral fibroblast SPARC expression and patient outcome with resectable pancreatic adenocarcinoma. J Clin Oncol. 2007;25:319–25.CrossRefPubMed
31.
go back to reference Erkan M, Michalski CW, Rieder S, Reiser-Erkan C, Abiatari I, Kolb A, et al. The activated stroma index is a novel and independent prognostic marker in pancreatic ductal adenocarcinoma. Clin Gastroenterol Hepatol. 2008;6:1155–61.CrossRefPubMed Erkan M, Michalski CW, Rieder S, Reiser-Erkan C, Abiatari I, Kolb A, et al. The activated stroma index is a novel and independent prognostic marker in pancreatic ductal adenocarcinoma. Clin Gastroenterol Hepatol. 2008;6:1155–61.CrossRefPubMed
32.
go back to reference Mantoni TS, Schendel RR, Rodel F, Niedobitek G, Al-Assar O, Masamune A, et al. Stromal sparc expression and patient survival after chemoradiation for non-resectable pancreatic adenocarcinoma. Cancer Biol Ther. 2008;7:1806–15.CrossRefPubMed Mantoni TS, Schendel RR, Rodel F, Niedobitek G, Al-Assar O, Masamune A, et al. Stromal sparc expression and patient survival after chemoradiation for non-resectable pancreatic adenocarcinoma. Cancer Biol Ther. 2008;7:1806–15.CrossRefPubMed
33.
go back to reference Schmid-Kotsas A, Gross HJ, Menke A, Weidenbach H, Adler G, Siech M, et al. Lipopolysaccharide-activated macrophages stimulate the synthesis of collagen type I and c-fibronectin in cultured pancreatic stellate cells. Am J Pathol. 1999;155:1749–58.CrossRefPubMedPubMedCentral Schmid-Kotsas A, Gross HJ, Menke A, Weidenbach H, Adler G, Siech M, et al. Lipopolysaccharide-activated macrophages stimulate the synthesis of collagen type I and c-fibronectin in cultured pancreatic stellate cells. Am J Pathol. 1999;155:1749–58.CrossRefPubMedPubMedCentral
34.
go back to reference Ijichi H. Inhibition of CXCLs/CXCR2 axis in the tumor microenvironment might be a potent therapeutics for pancreatic cancer. Oncoimmunol. 2012;1:569–71.CrossRef Ijichi H. Inhibition of CXCLs/CXCR2 axis in the tumor microenvironment might be a potent therapeutics for pancreatic cancer. Oncoimmunol. 2012;1:569–71.CrossRef
35.
go back to reference Yogo Y, Fujishima S, Inoue T, Saito F, Shiomi T, Yamaguchi K, et al. Macrophage derived chemokine (CCL22), thymus and activation-regulated chemokine (CCL17), and CCR4 in idiopathic pulmonary fibrosis. Respir Res. 2009;10:80.CrossRefPubMedPubMedCentral Yogo Y, Fujishima S, Inoue T, Saito F, Shiomi T, Yamaguchi K, et al. Macrophage derived chemokine (CCL22), thymus and activation-regulated chemokine (CCL17), and CCR4 in idiopathic pulmonary fibrosis. Respir Res. 2009;10:80.CrossRefPubMedPubMedCentral
36.
37.
go back to reference Thompson RW, Pesce JT, Ramalingam T, Wilson MS, White S, Cheever AW, et al. Cationic amino acid transporter-2 regulates immunity by modulating arginase activity. PLoS Pathog. 2008;4:e1000023.CrossRefPubMedPubMedCentral Thompson RW, Pesce JT, Ramalingam T, Wilson MS, White S, Cheever AW, et al. Cationic amino acid transporter-2 regulates immunity by modulating arginase activity. PLoS Pathog. 2008;4:e1000023.CrossRefPubMedPubMedCentral
38.
go back to reference Ninichuk V, Gross O, Reichel C, Khandoga A, Pawar RD, Ciubar R, et al. Delayed chemokine receptor 1 blockade prolongs survival in collagen 4A3-deficient mice with Alport disease. J Am Soc Nephrol. 2005;16:977–85.CrossRefPubMed Ninichuk V, Gross O, Reichel C, Khandoga A, Pawar RD, Ciubar R, et al. Delayed chemokine receptor 1 blockade prolongs survival in collagen 4A3-deficient mice with Alport disease. J Am Soc Nephrol. 2005;16:977–85.CrossRefPubMed
39.
go back to reference Shek FW, Benyon RC, Walker FM, McCrudden PR, Pender SL, Williams EJ, et al. Expression of transforming growth factor-beta 1 by pancreatic stellate cells and its implications for matrix secretion and turnover in chronic pancreatitis. Am J Pathol. 2002;160:1787–98.CrossRefPubMedPubMedCentral Shek FW, Benyon RC, Walker FM, McCrudden PR, Pender SL, Williams EJ, et al. Expression of transforming growth factor-beta 1 by pancreatic stellate cells and its implications for matrix secretion and turnover in chronic pancreatitis. Am J Pathol. 2002;160:1787–98.CrossRefPubMedPubMedCentral
40.
go back to reference Phillips PA, Wu MJ, Kumar RK, Doherty E, McCarroll JA, Park S, et al. Cell migration: a novel aspect of pancreatic stellate cell biology. Gut. 2003;52:677–82.CrossRefPubMedPubMedCentral Phillips PA, Wu MJ, Kumar RK, Doherty E, McCarroll JA, Park S, et al. Cell migration: a novel aspect of pancreatic stellate cell biology. Gut. 2003;52:677–82.CrossRefPubMedPubMedCentral
41.
go back to reference Gao R, Brigstock DR. Connective tissue growth factor (CCN2) in rat pancreatic stellate cell function: integrin alpha5beta1 as a novel CCN2 receptor. Gastroenterology. 2005;129:1019–30.CrossRefPubMed Gao R, Brigstock DR. Connective tissue growth factor (CCN2) in rat pancreatic stellate cell function: integrin alpha5beta1 as a novel CCN2 receptor. Gastroenterology. 2005;129:1019–30.CrossRefPubMed
42.
go back to reference Aoki H, Ohnishi H, Hama K, Shinozaki S, Kita H, Osawa H, et al. Cyclooxygenase-2 is required for activated pancreatic stellate cells to respond to proinflammatory cytokines. Am J Physiol Cell Physiol. 2007;292:C259–68.CrossRefPubMed Aoki H, Ohnishi H, Hama K, Shinozaki S, Kita H, Osawa H, et al. Cyclooxygenase-2 is required for activated pancreatic stellate cells to respond to proinflammatory cytokines. Am J Physiol Cell Physiol. 2007;292:C259–68.CrossRefPubMed
43.
go back to reference Egeblad M, Werb Z. New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer. 2002;2:161–74.CrossRefPubMed Egeblad M, Werb Z. New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer. 2002;2:161–74.CrossRefPubMed
44.
go back to reference Giraudo E, Inoue M, Hanahan D. An amino-bisphosphonate targets MMP-9-expressing macrophages and angiogenesis to impair cervical carcinogenesis. J Clin Invest. 2004;114:623–33.CrossRefPubMedPubMedCentral Giraudo E, Inoue M, Hanahan D. An amino-bisphosphonate targets MMP-9-expressing macrophages and angiogenesis to impair cervical carcinogenesis. J Clin Invest. 2004;114:623–33.CrossRefPubMedPubMedCentral
45.
46.
go back to reference Bergers G, Brekken R, McMahon G, Vu TH, Itoh T, Tamaki K, et al. Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat Cell Biol. 2000;2:737–44.CrossRefPubMedPubMedCentral Bergers G, Brekken R, McMahon G, Vu TH, Itoh T, Tamaki K, et al. Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat Cell Biol. 2000;2:737–44.CrossRefPubMedPubMedCentral
48.
49.
go back to reference Newman AC, Hughes C. Macrophages and angiogenesis: a role for Wnt signaling. Vasc Cell. 2012;4:13–3. Newman AC, Hughes C. Macrophages and angiogenesis: a role for Wnt signaling. Vasc Cell. 2012;4:13–3.
51.
go back to reference Wei D, Wang L, He Y, Xiong HQ, Abbruzzese JL, Xie K. Celecoxib inhibits vascular endothelial growth factor expression in and reduces angiogenesis and metastasis of human pancreatic cancer via suppression of sp1 transcription factor activity. Cancer Res. 2004;64:2030–8.CrossRefPubMed Wei D, Wang L, He Y, Xiong HQ, Abbruzzese JL, Xie K. Celecoxib inhibits vascular endothelial growth factor expression in and reduces angiogenesis and metastasis of human pancreatic cancer via suppression of sp1 transcription factor activity. Cancer Res. 2004;64:2030–8.CrossRefPubMed
52.
go back to reference Kunnumakkara AB, Guha S, Krishnan S, Diagaradjane P, Gelovani J, Aggarwal BB. Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-κb–regulated gene products. Cancer Res. 2007;67:3853–61.CrossRefPubMed Kunnumakkara AB, Guha S, Krishnan S, Diagaradjane P, Gelovani J, Aggarwal BB. Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-κb–regulated gene products. Cancer Res. 2007;67:3853–61.CrossRefPubMed
53.
go back to reference Schmid MC, Avraamides CJ, Dippold HC, Franco I, Foubert P, Ellies LG, et al. Receptor tyrosine kinases and TLR/IL1Rs unexpectedly activate myeloid cell PI3Kγ, a single convergent point promoting tumor inflammation and progression. Cancer Cell. 2011;19:715–27.CrossRefPubMedPubMedCentral Schmid MC, Avraamides CJ, Dippold HC, Franco I, Foubert P, Ellies LG, et al. Receptor tyrosine kinases and TLR/IL1Rs unexpectedly activate myeloid cell PI3Kγ, a single convergent point promoting tumor inflammation and progression. Cancer Cell. 2011;19:715–27.CrossRefPubMedPubMedCentral
54.
go back to reference Schmid MC, Avraamides CJ, Foubert P, Shaked Y, Kang SW, Kerbel RS, et al. Combined blockade of integrin-α4β1 plus cytokines SDF-1α or IL-1β potently inhibits tumor inflammation and growth. Cancer Res. 2011;71:6965–75.CrossRefPubMedPubMedCentral Schmid MC, Avraamides CJ, Foubert P, Shaked Y, Kang SW, Kerbel RS, et al. Combined blockade of integrin-α4β1 plus cytokines SDF-1α or IL-1β potently inhibits tumor inflammation and growth. Cancer Res. 2011;71:6965–75.CrossRefPubMedPubMedCentral
55.
go back to reference Tugues S, Honjo S, König C, Noguer O, Hedlund M, Botling J, et al. Genetic deficiency in plasma protein HRG enhances tumor growth and metastasis by exacerbating immune escape and vessel abnormalization. Cancer Res. 2012;72:1953–63.CrossRefPubMed Tugues S, Honjo S, König C, Noguer O, Hedlund M, Botling J, et al. Genetic deficiency in plasma protein HRG enhances tumor growth and metastasis by exacerbating immune escape and vessel abnormalization. Cancer Res. 2012;72:1953–63.CrossRefPubMed
56.
go back to reference Sunderkötter C, Steinbrink K, Goebeler M, Bhardwaj R, Sorg C. Macrophages and angiogenesis. J Leukoc Biol. 1994;55:410–22.PubMed Sunderkötter C, Steinbrink K, Goebeler M, Bhardwaj R, Sorg C. Macrophages and angiogenesis. J Leukoc Biol. 1994;55:410–22.PubMed
57.
go back to reference Kindler HL, Friberg G, Singh DA, Locker G, Nattam S, Kozloff M, et al. Phase II trial of bevacizumab plus gemcitabine in patients with advanced pancreatic cancer. J Clin Oncol. 2005;23:8033–40.CrossRefPubMed Kindler HL, Friberg G, Singh DA, Locker G, Nattam S, Kozloff M, et al. Phase II trial of bevacizumab plus gemcitabine in patients with advanced pancreatic cancer. J Clin Oncol. 2005;23:8033–40.CrossRefPubMed
58.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
59.
60.
go back to reference Schioppa T, Uranchimeg B, Saccani A, Biswas SK, Doni A, Rapisarda A, et al. Regulation of the chemokine receptor CXCR4 by hypoxia. J Exp Med. 2003;198:1391–402.CrossRefPubMedPubMedCentral Schioppa T, Uranchimeg B, Saccani A, Biswas SK, Doni A, Rapisarda A, et al. Regulation of the chemokine receptor CXCR4 by hypoxia. J Exp Med. 2003;198:1391–402.CrossRefPubMedPubMedCentral
61.
go back to reference Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ. Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res. 2005;65:10946–51.CrossRefPubMed Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ. Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res. 2005;65:10946–51.CrossRefPubMed
62.
go back to reference Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci. 2003;100:3983–8.CrossRefPubMedPubMedCentral Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci. 2003;100:3983–8.CrossRefPubMedPubMedCentral
63.
go back to reference Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, et al. Identification and expansion of human colon-cancer-initiating cells. Nature. 2007;445:111–5.CrossRefPubMed Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, et al. Identification and expansion of human colon-cancer-initiating cells. Nature. 2007;445:111–5.CrossRefPubMed
65.
go back to reference Visvader JE, Lindeman GJ. Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer. 2008;8:755–68.CrossRefPubMed Visvader JE, Lindeman GJ. Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer. 2008;8:755–68.CrossRefPubMed
66.
67.
go back to reference Hermann PC, Huber SL, Herrler T, Aicher A, Ellwart JW, Guba M, et al. Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell. 2007;1:313–23.CrossRefPubMed Hermann PC, Huber SL, Herrler T, Aicher A, Ellwart JW, Guba M, et al. Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell. 2007;1:313–23.CrossRefPubMed
68.
go back to reference Ding J, Jin W, Chen C, Shao Z, Wu J. Tumor associated macrophage × cancer cell hybrids may acquire cancer stem cell properties in breast cancer. PLoS One. 2012;7:e41942.CrossRefPubMedPubMedCentral Ding J, Jin W, Chen C, Shao Z, Wu J. Tumor associated macrophage × cancer cell hybrids may acquire cancer stem cell properties in breast cancer. PLoS One. 2012;7:e41942.CrossRefPubMedPubMedCentral
69.
go back to reference Jinushi M, Chiba S, Yoshiyama H, Masutomi K, Kinoshita I, Dosaka-Akita H, et al. Tumor-associated macrophages regulate tumorigenicity and anticancer drug responses of cancer stem/initiating cells. Proc Natl Acad Sci. 2011;108:12425–30.CrossRefPubMedPubMedCentral Jinushi M, Chiba S, Yoshiyama H, Masutomi K, Kinoshita I, Dosaka-Akita H, et al. Tumor-associated macrophages regulate tumorigenicity and anticancer drug responses of cancer stem/initiating cells. Proc Natl Acad Sci. 2011;108:12425–30.CrossRefPubMedPubMedCentral
70.
go back to reference Andersen JB, Aaboe M, Borden E, Goloubeva O, Hassel B, Ørntoft TF. Stage-associated overexpression of the ubiquitin-like protein, ISG15, in bladder cancer. Br J Cancer. 2006;94:1465–71.CrossRefPubMedPubMedCentral Andersen JB, Aaboe M, Borden E, Goloubeva O, Hassel B, Ørntoft TF. Stage-associated overexpression of the ubiquitin-like protein, ISG15, in bladder cancer. Br J Cancer. 2006;94:1465–71.CrossRefPubMedPubMedCentral
71.
go back to reference Hoeller D, Hecker C-M, Dikic I. Ubiquitin and ubiquitin-like proteins in cancer pathogenesis. Nat Rev Cancer. 2006;6:776–88.CrossRefPubMed Hoeller D, Hecker C-M, Dikic I. Ubiquitin and ubiquitin-like proteins in cancer pathogenesis. Nat Rev Cancer. 2006;6:776–88.CrossRefPubMed
72.
go back to reference Sainz Jr B, Martin B, Tatari M, Heeschen C, Guerra S. ISG15 is a critical microenvironmental factor for pancreatic cancer stem cells. Cancer Res. 2014;74:7309–20.CrossRefPubMed Sainz Jr B, Martin B, Tatari M, Heeschen C, Guerra S. ISG15 is a critical microenvironmental factor for pancreatic cancer stem cells. Cancer Res. 2014;74:7309–20.CrossRefPubMed
73.
go back to reference Mitchem JB, Brennan DJ, Knolhoff BL, Belt BA, Zhu Y, Sanford DE, et al. Targeting tumor-infiltrating macrophages decreases tumor-initiating cells, relieves immunosuppression, and improves chemotherapeutic responses. Cancer Res. 2013;73:1128–41.CrossRefPubMed Mitchem JB, Brennan DJ, Knolhoff BL, Belt BA, Zhu Y, Sanford DE, et al. Targeting tumor-infiltrating macrophages decreases tumor-initiating cells, relieves immunosuppression, and improves chemotherapeutic responses. Cancer Res. 2013;73:1128–41.CrossRefPubMed
74.
go back to reference Pylayeva-Gupta Y, Lee KE, Hajdu CH, Miller G, Bar-Sagi D. Oncogenic Kras-induced GM-CSF production promotes the development of pancreatic neoplasia. Cancer Cell. 2012;21:836–47.CrossRefPubMedPubMedCentral Pylayeva-Gupta Y, Lee KE, Hajdu CH, Miller G, Bar-Sagi D. Oncogenic Kras-induced GM-CSF production promotes the development of pancreatic neoplasia. Cancer Cell. 2012;21:836–47.CrossRefPubMedPubMedCentral
75.
go back to reference Vane JR, Botting RM. A better understanding of anti-inflammatory drugs based on isoforms of cyclooxygenase (COX-1 and COX-2). Adv Prostaglandin Thromboxane Leukot Res. 1995;23:41–8.PubMed Vane JR, Botting RM. A better understanding of anti-inflammatory drugs based on isoforms of cyclooxygenase (COX-1 and COX-2). Adv Prostaglandin Thromboxane Leukot Res. 1995;23:41–8.PubMed
76.
go back to reference Vendramini-Costa DB, Carvalho JE. Molecular link mechanisms between inflammation and cancer. Curr Pharm Des. 2012;18:3831–52.CrossRefPubMed Vendramini-Costa DB, Carvalho JE. Molecular link mechanisms between inflammation and cancer. Curr Pharm Des. 2012;18:3831–52.CrossRefPubMed
77.
go back to reference Colegio OR, Ngoc-Quynh C, Szabo AL, Chu T, Rhebergen AM, Jairam V, et al. Functional polarization of tumour-associated macrophages by tumour-derived lactic acid. Nature. 2014;513:559−+.CrossRefPubMedPubMedCentral Colegio OR, Ngoc-Quynh C, Szabo AL, Chu T, Rhebergen AM, Jairam V, et al. Functional polarization of tumour-associated macrophages by tumour-derived lactic acid. Nature. 2014;513:559−+.CrossRefPubMedPubMedCentral
78.
go back to reference Rauh MJ, Ho V, Pereira C, Sham A, Sly LM, Lam V, et al. SHIP represses the generation of alternatively activated macrophages. Immunity. 2005;23:361–74.CrossRefPubMed Rauh MJ, Ho V, Pereira C, Sham A, Sly LM, Lam V, et al. SHIP represses the generation of alternatively activated macrophages. Immunity. 2005;23:361–74.CrossRefPubMed
79.
go back to reference Luo Y, Zhou H, Krueger J, Kaplan C, Lee SH, Dolman C, et al. Targeting tumor-associated macrophages as a novel strategy against breast cancer. J Clin Invest. 2006;116:2132–41.CrossRefPubMedPubMedCentral Luo Y, Zhou H, Krueger J, Kaplan C, Lee SH, Dolman C, et al. Targeting tumor-associated macrophages as a novel strategy against breast cancer. J Clin Invest. 2006;116:2132–41.CrossRefPubMedPubMedCentral
80.
go back to reference Allavena P, Signorelli M, Chieppa M, Erba E, Bianchi G, Marchesi F, et al. Anti-inflammatory properties of the novel antitumor agent yondelis (trabectedin): inhibition of macrophage differentiation and cytokine production. Cancer Res. 2005;65:2964–71.CrossRefPubMed Allavena P, Signorelli M, Chieppa M, Erba E, Bianchi G, Marchesi F, et al. Anti-inflammatory properties of the novel antitumor agent yondelis (trabectedin): inhibition of macrophage differentiation and cytokine production. Cancer Res. 2005;65:2964–71.CrossRefPubMed
Metadata
Title
Functional significance of macrophages in pancreatic cancer biology
Authors
Hai Hu
Feng Jiao
Ting Han
Li-Wei Wang
Publication date
01-12-2015
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 12/2015
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4127-2

Other articles of this Issue 12/2015

Tumor Biology 12/2015 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine