1 Saif, M. W. Pancreatic neoplasm in 2011: an update. JOP 12, 316–321 (2011).

2 Chan, A., Diamandis, E. P. & Blasutig, I. M. Strategies for discovering novel pancreatic cancer biomarkers. J. Proteomics 81, 126–134 (2013).

3 Fesinmeyer, M. D., Austin, M. A., Li, C. I., De Roos, A. J. & Bowen, D. J. Differences in survival by histologic type of pancreatic cancer. Cancer Epidemiol. Biomarkers Prev. 14, 1766–1773 (2005).

4 Arscott, W. T. & Camphausen, K. A. EGFR isoforms in exosomes as a novel method for biomarker discovery in pancreatic cancer. Biomarkers Med. 5, 821 (2011).

5 Record, M., Carayon, K., Poirot, M. & Silvente-Poirot, S. Exosomes as new vesicular lipid transporters involved in cell–cell communication and various pathophysiologies. Biochim. Biophys. Acta 1841, 108–120 (2014).

6 El Andaloussi, S., Mager, I., Breakefield, X. O. & Wood, M. J. Extracellular vesicles: biology and emerging therapeutic opportunities. Nat. Rev. Drug Discov. 12, 347–357 (2013).

7 Choi, D. S., Kim, D. K., Kim, Y. K. & Gho, Y. S. Proteomics, transcriptomics and lipidomics of exosomes and ectosomes. Proteomics 13, 1554–1571 (2013).

8 Martins, V. R., Dias, M. S. & Hainaut, P. Tumor-cell-derived microvesicles as carriers of molecular information in cancer. Curr. Opin. Oncol. 25, 66–75 (2013).

9 Peinado, H., Lavotshkin, S. & Lyden, D. The secreted factors responsible for pre-metastatic niche formation: old sayings and new thoughts. Semin. Cancer Biol. 21, 139–146 (2011).

10 Thakur, B. K. et al. Double-stranded DNA in exosomes: a novel biomarker in cancer detection. Cell Res. 24, 766–769 (2014).

11 Tetta, C., Ghigo, E., Silengo, L., Deregibus, M. C. & Camussi, G. Extracellular vesicles as an emerging mechanism of cell-to-cell communication. Endocrine 44, 11–19 (2013).

12 Valadi, H. et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol. 9, 654–659 (2007).

13 Zoller, M. Pancreatic cancer diagnosis by free and exosomal miRNA. World J. Gastrointest. Pathophysiol. 4, 74–90 (2013).

14 Kaplan, R. N. et al. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438, 820–827 (2005).

15 Sceneay, J., Smyth, M. J. & Moller, A. The pre-metastatic niche: finding common ground. Cancer Metastasis Rev. 32, 449–464 (2013).

16 Peinado, H. et al. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat. Med. 18, 883–891 (2012).

17 Hood, J. L., San, R. S. & Wickline, S. A. Exosomes released by melanoma cells prepare sentinel lymph nodes for tumor metastasis. Cancer Res. 71, 3792–3801 (2011).

18 Corbett, T. H. et al. Induction and chemotherapeutic response of two transplantable ductal adenocarcinomas of the pancreas in C57BL/6 mice. Cancer Res. 44, 717–726 (1984).

19 Little, E. C. et al. Novel immunocompetent murine models representing advanced local and metastatic pancreatic cancer. J. Surg. Res. 176, 359–366 (2012).

20 Hingorani, S. R. et al. Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell 7, 469–483 (2005).

21 Rhim, A. D. et al. EMT and dissemination precede pancreatic tumor formation. Cell 148, 349–361 (2012).

22 Achyut, B. R. & Yang, L. Transforming growth factor-β in the gastrointestinal and hepatic tumor microenvironment. Gastroenterology 141, 1167–1178 (2011).

23 Hayashi, H. & Sakai, T. Biological significance of local TGF-β activation in liver diseases. Front. Physiol. 3, 12 (2012).

24 Wight, T. N. & Potter-Perigo, S. The extracellular matrix: an active or passive player in fibrosis? Am. J. Physiol. Gastrointest. Liver Physiol. 301, G950–G955 (2011).

25 Gressner, A. M., Weiskirchen, R., Breitkopf, K. & Dooley, S. Roles of TGF-β in hepatic fibrosis. Front. Biosci. 7, d793–d807 (2002).

26 Cong, M., Iwaisako, K., Jiang, C. & Kisseleva, T. Cell signals influencing hepatic fibrosis. Int. J. Hepatol. 2012, 158547 (2012).

27 Kawelke, N. et al. Fibronectin protects from excessive liver fibrosis by modulating the availability of and responsiveness of stellate cells to active TGF-β. PLoS ONE 6, e28181 (2011).

28 Xu, G. et al. Gene expression and synthesis of fibronectin isoforms in rat hepatic stellate cells. Comparison with liver parenchymal cells and skin fibroblasts. J. Pathol. 183, 90–98 (1997).

29 Tojo, M. et al. The ALK-5 inhibitor A-83-01 inhibits Smad signaling and epithelial-to-mesenchymal transition by transforming growth factor-β. Cancer Sci. 96, 791–800 (2005).

30 Duffield, J. S. et al. Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair. J. Clin. Invest. 115, 56–65 (2005).

31 Lau, C. et al. Role of pancreatic cancer-derived exosomes in salivary biomarker development. J. Biol. Chem. 288, 26888–26897 (2013).

32 Heinrichs, D. et al. Macrophage migration inhibitory factor (MIF) exerts antifibrotic effects in experimental liver fibrosis via CD74. Proc. Natl Acad. Sci. USA 108, 17444–17449 (2011).

33 Barnes, M. A. et al. Macrophage migration inhibitory factor contributes to ethanol-induced liver injury by mediating cell injury, steatohepatitis, and steatosis. Hepatology 57, 1980–1991 (2013).

34 Funamizu, N. et al. Macrophage migration inhibitory factor induces epithelial to mesenchymal transition, enhances tumor aggressiveness and predicts clinical outcome in resected pancreatic ductal adenocarcinoma. Int. J. Cancer 132, 785–794 (2013).

35 Nanji, A. A. et al. Macrophage migration inhibitory factor expression in male and female ethanol-fed rats. J. Interferon Cytokine Res. 21, 1055–1062 (2001).

36 Shin, H. N., Moon, H. H. & Ku, J. L. Stromal cell-derived factor-1α and macrophage migration-inhibitory factor induce metastatic behavior in CXCR4-expressing colon cancer cells. Int. J. Mol. Med. 30, 1537–1543 (2012).

37 Zhang, H. Y. et al. Macrophage migration inhibitory factor expression correlates with inflammatory changes in human chronic hepatitis B infection. Liver Int. 25, 571–579 (2005).

38 Adamali, H. et al. Macrophage migration inhibitory factor enzymatic activity, lung inflammation, and cystic fibrosis. Am. J. Respir. Crit. Care Med. 186, 162–169 (2012).

39 Kobayashi, S., Nishihira, J., Watanabe, S. & Todo, S. Prevention of lethal acute hepatic failure by antimacrophage migration inhibitory factor antibody in mice treated with bacille Calmette-Guerin and lipopolysaccharide. Hepatology 29, 1752–1759 (1999).

40 Yaddanapudi, K. et al. Control of tumor-associated macrophage alternative activation by macrophage migration inhibitory factor. J. Immunol. 190, 2984–2993 (2013).

41 Chen, P. F. et al. ISO-1, a macrophage migration inhibitory factor antagonist, inhibits airway remodeling in a murine model of chronic asthma. Mol. Med. 16, 400–408 (2010).

42 Javle, M. et al. Biomarkers of TGF-β signaling pathway and prognosis of pancreatic cancer. PLoS ONE 9, e85942 (2014).

43 Ellermeier, J. et al. Therapeutic efficacy of bifunctional siRNA combining TGF-β1 silencing with RIG-I activation in pancreatic cancer. Cancer Res. 73, 1709–1720 (2013).

44 Gaspar, N. J. et al. Inhibition of transforming growth factor β signaling reduces pancreatic adenocarcinoma growth and invasiveness. Mol. Pharmacol. 72, 152–161 (2007).

45 Melisi, D. et al. LY2109761, a novel transforming growth factor β receptor type I and type II dual inhibitor, as a therapeutic approach to suppressing pancreatic cancer metastasis. Mol. Cancer Ther. 7, 829–840 (2008).

46 Pickup, M., Novitskiy, S. & Moses, H. L. The roles of TGFβ in the tumour microenvironment. Nat. Rev. Cancer 13, 788–799 (2013).

47 Ijichi, H. et al. Aggressive pancreatic ductal adenocarcinoma in mice caused by pancreas-specific blockade of transforming growth factor-β signaling in cooperation with active Kras expression. Genes Dev. 20, 3147–3160 (2006).

48 Hezel, A. F. et al. TGF-β and αvβ6 integrin act in a common pathway to suppress pancreatic cancer progression. Cancer Res. 72, 4840–4845 (2012).

49 Bayon, L. G. et al. Role of Kupffer cells in arresting circulating tumor cells and controlling metastatic growth in the liver. Hepatology 23, 1224–1231 (1996).

50 Kruse, J. et al. Macrophages promote tumour growth and liver metastasis in an orthotopic syngeneic mouse model of colon cancer. Int. J. Colorectal Dis. 28, 1337–1349 (2013).

51 Wen, S. W., Ager, E. I. & Christophi, C. Bimodal role of Kupffer cells during colorectal cancer liver metastasis. Cancer Biol. Ther. 14, 606–613 (2013).

52 Grzesiak, J. J. et al. Knockdown of the β(1) integrin subunit reduces primary tumor growth and inhibits pancreatic cancer metastasis. Int. J. Cancer 129, 2905–2915 (2011).

53 Saito, N. et al. Inhibition of hepatic metastasis in mice treated with cell-binding domain of human fibronectin and angiogenesis inhibitor TNP-470. Int. J. Clin. Oncol. 6, 215–220 (2001).

54 Zvibel, I., Halpern, Z. & Papa, M. Extracellular matrix modulates expression of growth factors and growth-factor receptors in liver-colonizing colon-cancer cell lines. Int. J. Cancer 77, 295–301 (1998).

55 Porembka, M. R. et al. Pancreatic adenocarcinoma induces bone marrow mobilization of myeloid-derived suppressor cells which promote primary tumor growth. Cancer Immunol. Immunother. 61, 1373–1385 (2012).

56 Yamamoto, M. et al. TSU68 prevents liver metastasis of colon cancer xenografts by modulating the premetastatic niche. Cancer Res. 68, 9754–9762 (2008).

57 Zhang, Y., Davis, C., Ryan, J., Janney, C. & Pena, M. M. Development and characterization of a reliable mouse model of colorectal cancer metastasis to the liver. Clin. Exp. Metastasis 30, 903–918 (2013).

58 Seubert, B. et al. Tissue inhibitor of metalloproteinases (TIMP)-1 creates a premetastatic niche in the liver through SDF-1/CXCR4-dependent neutrophil recruitment in mice. Hepatology 61, 238–248 (2015).

59 Kato, R. et al. A new type of antimetastatic peptide derived from fibronectin. Clin. Cancer Res. 8, 2455–2462 (2002).

60 Bissell, D. M. Therapy for hepatic fibrosis: revisiting the preclinical models. Clin. Res. Hepatol. Gastroenterol. 35, 521–525 (2011).

61 Korpal, M. & Kang, Y. Targeting the transforming growth factor-β signalling pathway in metastatic cancer. Eur. J. Cancer 46, 1232–1240 (2010).

62 Noy, R. & Pollard, J. W. Tumor-associated macrophages: from mechanisms to therapy. Immunity 41, 49–61 (2014).

63 Gu, G., Brown, J. R. & Melton, D. A. Direct lineage tracing reveals the ontogeny of pancreatic cell fates during mouse embryogenesis. Mech. Dev. 120, 35–43 (2003).

64 Zhong, S. et al. High throughput illuma strand-specific RNA sequencing library preparation. Cold Spring Harb. Protoc. 2011, 940–949 (2011).

65 Sakai, T. et al. Plasma fibronectin supports neuronal survival and reduces brain injury following transient focal cerebral ischemia but is not essential for skin-wound healing and hemostasis. Nat. Med. 7, 324–330 (2001).

66 Suemizu, H. et al. A versatile technique for the in vivo imaging of human tumor xenografts using near-infrared fluorochrome-conjugated macromolecule probes. PLoS ONE 8, e82708 (2013).