Pancreatic Cancer Cells Invasiveness is Mainly Affected by Interleukin-1β not by Transforming Growth Factor-β1

Background We investigated in vitro whether IL-1β and TGF-β1 affect pancreatic cancer cell growth, adhesion to the extracellular matrix and Matrigel invasion. Materials and methods Adhesion to fibronectin, laminin and type I collagen, and Matrigel invasion after stimulation with saline, IL-1β and TGF-β1 were evaluated using three primary and three metastatic pancreatic cancer cell lines. Results Extracellular matrix adhesion of control cells varied independently of the metastatic characteristics of the studied cell lines, whereas Matrigel invasion of control cells was partly correlated with the in vivo metastatic potential. IL-1β did not influence extracellular matrix adhesion, whereas it significantly enhanced the invasiveness of three of the six cell lines. TGF-β1 affected the adhesion of one cell line, and exerted contrasting effects on Matrigel invasion of different cell lines. Conclusions IL-1β enhances the invasive capacity of pancreatic cancer cells, whereas TGF-β1 has paradoxical effects on pancreatic cancer cells; this makes it difficult to interfere with TGF-β1 signaling in pancreatic cancer treatment.

[1]  B. Sipos,et al.  Tumor Stroma Interactions Induce Chemoresistance in Pancreatic Ductal Carcinoma Cells Involving Increased Secretion and Paracrine Effects of Nitric Oxide and Interleukin-1β , 2004, Cancer Research.

[2]  松尾 洋一 Enhanced angiogenesis due to inflammatory cytokines from pancreatic cancer cell lines and relation to metastatic potential , 2004 .

[3]  M. Plebani,et al.  Suicide gene therapy with HSV-TK in pancreatic cancer has no effect in vivo in a mouse model. , 2003, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[4]  H. Sawai,et al.  Interleukin-1α Enhances Integrin α6β1 Expression and Metastatic Capability of Human Pancreatic Cancer , 2003, Oncology.

[5]  M. Löhr,et al.  A comprehensive characterization of pancreatic ductal carcinoma cell lines: towards the establishment of an in vitro research platform , 2003, Virchows Archiv.

[6]  M. Höglund,et al.  Pancreatic carcinoma cell lines with SMAD4 inactivation show distinct expression responses to TGFB1 , 2003, Genes, chromosomes & cancer.

[7]  Y. Iwakura,et al.  IL-1 is required for tumor invasiveness and angiogenesis , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[8]  H. Sawai,et al.  Enhancement of integrins by interleukin‐1α, and their relationship with metastatic and invasive behavior of human pancreatic ductal adenocarcinoma cells , 2003, Journal of surgical oncology.

[9]  K. Venkatasubbarao,et al.  Rap1 reverses transcriptional repression of TGF‐β type II receptor by a mechanism involving AP‐1 in the human pancreatic cancer cell line, UK Pan‐1 , 2003, Journal of cellular physiology.

[10]  Leif E. Peterson,et al.  Effect of interleukin 1 polymorphisms on gastric mucosal interleukin 1β production in Helicobacter pylori infection , 2002 .

[11]  M. Rugge,et al.  Helicobacter pylori virulence genes and host IL-1RN and IL-1beta genes interplay in favouring the development of peptic ulcer and intestinal metaplasia. , 2002, Cytokine.

[12]  L. Wakefield,et al.  TGF-β signaling: positive and negative effects on tumorigenesis , 2002 .

[13]  F. Liu SMAD4/DPC4 and pancreatic cancer survival. Commentary re: M. Tascilar et al., The SMAD4 protein and prognosis of pancreatic ductal adenocarcinoma. Clin. Cancer Res., 7: 4115-4121, 2001. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[14]  C. Hill,et al.  Loss of Smad4 Function in Pancreatic Tumors , 2001, The Journal of Biological Chemistry.

[15]  M. Ohira,et al.  TGF-beta1 promotes liver metastasis of pancreatic cancer by modulating the capacity of cellular invasion. , 2001, International journal of oncology.

[16]  Allan Balmain,et al.  TGF-β signaling in tumor suppression and cancer progression , 2001, Nature Genetics.

[17]  T. Gress,et al.  TGF‐β–induced invasiveness of pancreatic cancer cells is mediated by matrix metalloproteinase‐2 and the urokinase plasminogen activator system , 2001, International journal of cancer.

[18]  B. Nicke,et al.  Smad4 mediates activation of mitogen-activated protein kinases by TGF-beta in pancreatic acinar cells. , 2001, American journal of physiology. Cell physiology.

[19]  B Johansson,et al.  Altered expression of TGFB receptors and mitogenic effects of TGFB in pancreatic carcinomas. , 2001, International journal of oncology.

[20]  A. Balmain,et al.  TGF-β signaling in tumor suppression and cancer progression , 2001, Nature Genetics.

[21]  J. Massagué,et al.  How cells read TGF-β signals , 2000, Nature Reviews Molecular Cell Biology.

[22]  O. Volpert,et al.  Smad4/DPC4-mediated tumor suppression through suppression of angiogenesis. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[23]  A. Wells,et al.  Tumor invasion: role of growth factor-induced cell motility. , 2000, Advances in cancer research.

[24]  J. Massagué How cells read TGF-beta signals. , 2000, Nature reviews. Molecular cell biology.

[25]  M. Plebani,et al.  Cytokines modulate MIA PaCa 2 and CAPAN-1 adhesion to extracellular matrix proteins. , 1999, Pancreas.

[26]  T. Gress,et al.  Invasion and metastasis in pancreatic cancer. , 1999, Annals of oncology : official journal of the European Society for Medical Oncology.

[27]  R. Hruban,et al.  Genetic alterations of the transforming growth factor beta receptor genes in pancreatic and biliary adenocarcinomas. , 1998, Cancer research.

[28]  D. Berger,et al.  The Effect of Thrombospondin-1 and TGF-β1 on Pancreatic Cancer Cell Invasion , 1998 .

[29]  M. Pepper,et al.  Transforming growth factor-beta: vasculogenesis, angiogenesis, and vessel wall integrity. , 1997, Cytokine & growth factor reviews.

[30]  M. Plebani,et al.  Insulin-like growth factor-I, interleukin-1 α and β in pancreatic cancer: role in tumor invasiveness and associated diabetes , 1995 .

[31]  M. Plebani,et al.  Insulin-like growth factor-I, interleukin-1 alpha and beta in pancreatic cancer: role in tumor invasiveness and associated diabetes. , 1995, International journal of clinical & laboratory research.

[32]  Brooks Jw,et al.  Interleukin-1 signal transduction. , 1994 .

[33]  C. Dinarello,et al.  The biological properties of interleukin-1. , 1994, European cytokine network.

[34]  C. Dinarello,et al.  Interleukin-1 receptor blockade reduces the number and size of murine B16 melanoma hepatic metastases. , 1994, Cancer research.

[35]  H. Friess,et al.  Enhanced expression of transforming growth factor β isoforms in pancreatic cancer correlates with decreased survival , 1993 .

[36]  R. L. Baldwin,et al.  Growth inhibition of human pancreatic carcinoma cells by transforming growth factor beta-1. , 1993, Growth factors.

[37]  F. Breviario,et al.  Interleukin 1 promotes tumor cell adhesion to cultured human endothelial cells. , 1988, The Journal of clinical investigation.

[38]  Y Iwamoto,et al.  A rapid in vitro assay for quantitating the invasive potential of tumor cells. , 1987, Cancer research.