Skip to main content
Erschienen in: Journal of Gastrointestinal Cancer 1-2/2009

01.06.2009 | REVIEW ARTICLE

Interplay of Tumor Microenvironment Cell Types with Parenchymal Cells in Pancreatic Cancer Development and Therapeutic Implications

verfasst von: Praveen Guturu, Vijay Shah, Raul Urrutia

Erschienen in: Journal of Gastrointestinal Cancer | Ausgabe 1-2/2009

Einloggen, um Zugang zu erhalten

Abstract

Introduction

The process of “induction,” namely, the formation of a tissue by the functional interaction between the epithelial layer and the stroma, is key for the development of many organs, in particular to the pancreas.

Discussion

In diseases like pancreatic cancer, most studies performed to date, in the area of pancreatic cancer, have focused on studying epithelial cells and their contribution to this disease. Strikingly, until recently, the stroma that surrounds cancer cells in pancreatic tumors (desmoplastic reaction–tumor microenvironment) has remained an underrepresented area of research. However, several laboratories are increasingly posing questions as what is the role of this tumor microenvironment in the development and progression of this fatal disease. Therefore, in the current article, we define and describe the components of this desmoplastic reaction and the pancreatic tumor microenvironment and briefly review advances being made. More importantly, we highlight the urgent need of research in this field.

Conclusion

We anticipate that, because of the paucity of knowledge on this subject, studies on the pancreatic tumor microenvironment will bring new concepts which will ultimately impact in designing new diagnosis and treatment for this disease.
Literatur
2.
Zurück zum Zitat Schneider G, Hamacher R, Eser S, Friess H, Schmid RM, Saur D. Molecular biology of pancreatic cancer—new aspects and targets. Anticancer Res. 2008;28:1541–50.PubMed Schneider G, Hamacher R, Eser S, Friess H, Schmid RM, Saur D. Molecular biology of pancreatic cancer—new aspects and targets. Anticancer Res. 2008;28:1541–50.PubMed
5.
6.
Zurück zum Zitat Mulkeen AL, Yoo PS, Cha C. Less common neoplasms of the pancreas. World J Gastroenterol. 2006;12:3180–5.PubMed Mulkeen AL, Yoo PS, Cha C. Less common neoplasms of the pancreas. World J Gastroenterol. 2006;12:3180–5.PubMed
11.
18.
Zurück zum Zitat Clark CE, Beatty GL, Vonderheide RH. Immunosurveillance of pancreatic adenocarcinoma: insights from genetically engineered mouse models of cancer. Cancer Lett. 2008;279:1–7.PubMedCrossRef Clark CE, Beatty GL, Vonderheide RH. Immunosurveillance of pancreatic adenocarcinoma: insights from genetically engineered mouse models of cancer. Cancer Lett. 2008;279:1–7.PubMedCrossRef
19.
Zurück zum Zitat Guerra C, Schuhmacher AJ, Canamero M, Grippo PJ, Verdaguer L, Perez-Gallego L, et al. Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice. Cancer Cell. 2007;11:291–302. doi:10.1016/j.ccr.2007.01.012.PubMedCrossRef Guerra C, Schuhmacher AJ, Canamero M, Grippo PJ, Verdaguer L, Perez-Gallego L, et al. Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice. Cancer Cell. 2007;11:291–302. doi:10.​1016/​j.​ccr.​2007.​01.​012.PubMedCrossRef
20.
Zurück zum Zitat Monti P, Leone BE, Marchesi F, Balzano G, Zerbi A, Scaltrini F, et al. The CC chemokine MCP-1/CCL2 in pancreatic cancer progression: regulation of expression and potential mechanisms of antimalignant activity. Cancer Res. 2003;63:7451–61.PubMed Monti P, Leone BE, Marchesi F, Balzano G, Zerbi A, Scaltrini F, et al. The CC chemokine MCP-1/CCL2 in pancreatic cancer progression: regulation of expression and potential mechanisms of antimalignant activity. Cancer Res. 2003;63:7451–61.PubMed
21.
Zurück zum Zitat Mytar B, Baj-Krzyworzeka M, Majka M, Stankiewicz D, Zembala M. Human monocytes both enhance and inhibit the growth of human pancreatic cancer in SCID mice. Anticancer Res. 2008;28:187–92.PubMed Mytar B, Baj-Krzyworzeka M, Majka M, Stankiewicz D, Zembala M. Human monocytes both enhance and inhibit the growth of human pancreatic cancer in SCID mice. Anticancer Res. 2008;28:187–92.PubMed
22.
Zurück zum Zitat Esposito I, Menicagli M, Funel N, Bergmann F, Boggi U, Mosca F, et al. Inflammatory cells contribute to the generation of an angiogenic phenotype in pancreatic ductal adenocarcinoma. J Clin Pathol. 2004;57:630–6. doi:10.1136/jcp. 2003.014498.PubMedCrossRef Esposito I, Menicagli M, Funel N, Bergmann F, Boggi U, Mosca F, et al. Inflammatory cells contribute to the generation of an angiogenic phenotype in pancreatic ductal adenocarcinoma. J Clin Pathol. 2004;57:630–6. doi:10.​1136/​jcp.​ 2003.​014498.PubMedCrossRef
24.
Zurück zum Zitat Calderon B, Suri A, Miller MJ, Unanue ER. Dendritic cells in islets of Langerhans constitutively present beta cell-derived peptides bound to their class II MHC molecules. Proc Natl Acad Sci U S A. 2008;105:6121–6. doi:10.1073/pnas.0801973105.PubMedCrossRef Calderon B, Suri A, Miller MJ, Unanue ER. Dendritic cells in islets of Langerhans constitutively present beta cell-derived peptides bound to their class II MHC molecules. Proc Natl Acad Sci U S A. 2008;105:6121–6. doi:10.​1073/​pnas.​0801973105.PubMedCrossRef
29.
Zurück zum Zitat Zhu Z, Kleeff J, Kayed H, Wang L, Korc M, Buchler MW, et al. Nerve growth factor and enhancement of proliferation, invasion, and tumorigenicity of pancreatic cancer cells. Mol Carcinog. 2002;35:138–47. doi:10.1002/mc.10083.PubMedCrossRef Zhu Z, Kleeff J, Kayed H, Wang L, Korc M, Buchler MW, et al. Nerve growth factor and enhancement of proliferation, invasion, and tumorigenicity of pancreatic cancer cells. Mol Carcinog. 2002;35:138–47. doi:10.​1002/​mc.​10083.PubMedCrossRef
31.
Zurück zum Zitat Ceyhan GO, Bergmann F, Kadihasanoglu M, Altintas B, Demir IE, Hinz U, et al. Pancreatic neuropathy and neuropathic pain—a comprehensive pathomorphological study of 546 cases. Gastroenterology. 2009;136:177.e1–86.e1.CrossRef Ceyhan GO, Bergmann F, Kadihasanoglu M, Altintas B, Demir IE, Hinz U, et al. Pancreatic neuropathy and neuropathic pain—a comprehensive pathomorphological study of 546 cases. Gastroenterology. 2009;136:177.e1–86.e1.CrossRef
33.
Zurück zum Zitat Phillips PA, McCarroll JA, Park S, Wu MJ, Pirola R, Korsten M, et al. Rat pancreatic stellate cells secrete matrix metalloproteinases: implications for extracellular matrix turnover. Gut. 2003;52:275–82. doi:10.1136/gut.52.2.275.PubMedCrossRef Phillips PA, McCarroll JA, Park S, Wu MJ, Pirola R, Korsten M, et al. Rat pancreatic stellate cells secrete matrix metalloproteinases: implications for extracellular matrix turnover. Gut. 2003;52:275–82. doi:10.​1136/​gut.​52.​2.​275.PubMedCrossRef
36.
Zurück zum Zitat Cartwright T, Richards DA, Boehm KA. Cancer of the pancreas: are we making progress? A review of studies in the US Oncology Research Network. Cancer Control. 2008;15:308–13.PubMed Cartwright T, Richards DA, Boehm KA. Cancer of the pancreas: are we making progress? A review of studies in the US Oncology Research Network. Cancer Control. 2008;15:308–13.PubMed
38.
Zurück zum Zitat Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007;25:1960–6. doi:10.1200/JCO.2006.07.9525.PubMedCrossRef Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007;25:1960–6. doi:10.​1200/​JCO.​2006.​07.​9525.PubMedCrossRef
40.
Zurück zum Zitat Gaspar NJ, Li L, Kapoun AM, Medicherla S, Reddy M, Li G, et al. Inhibition of transforming growth factor beta signaling reduces pancreatic adenocarcinoma growth and invasiveness. Mol Pharmacol. 2007;72:152–61. doi:10.1124/mol.106.029025.PubMedCrossRef Gaspar NJ, Li L, Kapoun AM, Medicherla S, Reddy M, Li G, et al. Inhibition of transforming growth factor beta signaling reduces pancreatic adenocarcinoma growth and invasiveness. Mol Pharmacol. 2007;72:152–61. doi:10.​1124/​mol.​106.​029025.PubMedCrossRef
41.
Zurück zum Zitat Aikawa T, Gunn J, Spong SM, Klaus SJ, Korc M. Connective tissue growth factor-specific antibody attenuates tumor growth, metastasis, and angiogenesis in an orthotopic mouse model of pancreatic cancer. Mol Cancer Ther. 2006;5:1108–16. doi:10.1158/1535-7163.MCT-05-0516.PubMedCrossRef Aikawa T, Gunn J, Spong SM, Klaus SJ, Korc M. Connective tissue growth factor-specific antibody attenuates tumor growth, metastasis, and angiogenesis in an orthotopic mouse model of pancreatic cancer. Mol Cancer Ther. 2006;5:1108–16. doi:10.​1158/​1535-7163.​MCT-05-0516.PubMedCrossRef
43.
Zurück zum Zitat Kindler H, Niedzwiecki D, Hollis D. A double-blind, placebo-controlled, randomized phase III trial of gemcitabine (G) plus bevacizumab (B) versus gemcitabine plus placebo (P) in patients (pts) with advanced pancreatic cancer (PC): a preliminary analysis of Cancer and Leukemia. J Clin Oncol. 2007;25:4508. (abstract). Kindler H, Niedzwiecki D, Hollis D. A double-blind, placebo-controlled, randomized phase III trial of gemcitabine (G) plus bevacizumab (B) versus gemcitabine plus placebo (P) in patients (pts) with advanced pancreatic cancer (PC): a preliminary analysis of Cancer and Leukemia. J Clin Oncol. 2007;25:4508. (abstract).
44.
Zurück zum Zitat Spano JP, Chodkiewicz C, Maurel J, Wong R, Wasan H, Barone C, et al. Efficacy of gemcitabine plus axitinib compared with gemcitabine alone in patients with advanced pancreatic cancer: an open-label randomised phase II study. Lancet. 2008;371:2101–8. doi:10.1016/S0140-6736(08)60661-3.PubMedCrossRef Spano JP, Chodkiewicz C, Maurel J, Wong R, Wasan H, Barone C, et al. Efficacy of gemcitabine plus axitinib compared with gemcitabine alone in patients with advanced pancreatic cancer: an open-label randomised phase II study. Lancet. 2008;371:2101–8. doi:10.​1016/​S0140-6736(08)60661-3.PubMedCrossRef
Metadaten
Titel
Interplay of Tumor Microenvironment Cell Types with Parenchymal Cells in Pancreatic Cancer Development and Therapeutic Implications
verfasst von
Praveen Guturu
Vijay Shah
Raul Urrutia
Publikationsdatum
01.06.2009
Verlag
Humana Press Inc
Erschienen in
Journal of Gastrointestinal Cancer / Ausgabe 1-2/2009
Print ISSN: 1941-6628
Elektronische ISSN: 1941-6636
DOI
https://doi.org/10.1007/s12029-009-9071-1

Weitere Artikel der Ausgabe 1-2/2009

Journal of Gastrointestinal Cancer 1-2/2009 Zur Ausgabe

Alphablocker schützt vor Miktionsproblemen nach der Biopsie

16.05.2024 alpha-1-Rezeptorantagonisten Nachrichten

Nach einer Prostatabiopsie treten häufig Probleme beim Wasserlassen auf. Ob sich das durch den periinterventionellen Einsatz von Alphablockern verhindern lässt, haben australische Mediziner im Zuge einer Metaanalyse untersucht.

Labor, CT-Anthropometrie zeigen Risiko für Pankreaskrebs

13.05.2024 Pankreaskarzinom Nachrichten

Gerade bei aggressiven Malignomen wie dem duktalen Adenokarzinom des Pankreas könnte Früherkennung die Therapiechancen verbessern. Noch jedoch klafft hier eine Lücke. Ein Studienteam hat einen Weg gesucht, sie zu schließen.

Viel pflanzliche Nahrung, seltener Prostata-Ca.-Progression

12.05.2024 Prostatakarzinom Nachrichten

Ein hoher Anteil pflanzlicher Nahrung trägt möglicherweise dazu bei, das Progressionsrisiko von Männern mit Prostatakarzinomen zu senken. In einer US-Studie war das Risiko bei ausgeprägter pflanzlicher Ernährung in etwa halbiert.

Alter verschlechtert Prognose bei Endometriumkarzinom

11.05.2024 Endometriumkarzinom Nachrichten

Ein höheres Alter bei der Diagnose eines Endometriumkarzinoms ist mit aggressiveren Tumorcharakteristika assoziiert, scheint aber auch unabhängig von bekannten Risikofaktoren die Prognose der Erkrankung zu verschlimmern.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.