Interleukin-13 exerts autocrine growth-promoting effects on human pancreatic cancer, and its expression correlates with a propensity for lymph node metastases

被引：31

作者：

Formentini, Andrea ^{[1
]}

Prokopchuk, Olga ^{[1
]}

Strater, Joern ^{[2
]}

Kleeff, Joerg ^{[3
]}

Grochola, Lukasz Filip ^{[1
]}

Leder, Gerd ^{[1
]}

Henne-Bruns, Doris ^{[1
]}

Korc, Murray ^{[4
,5
,6
,7
]}

Kornmann, Marko ^{[1
]}

机构：

[1] Univ Ulm, Clin Gen Visceral & Transplantat Surg, D-89075 Ulm, Germany

[2] Univ Ulm, Dept Pathol, D-89075 Ulm, Germany

[3] Heidelberg Univ, Dept Gen Surg, D-69120 Heidelberg, Germany

[4] Dartmouth Hitchcock Med Ctr, Dept Med, Hanover, NH 03755 USA

[5] Dartmouth Hitchcock Med Ctr, Dept Pharmacol, Hanover, NH 03755 USA

[6] Dartmouth Hitchcock Med Ctr, Dept Toxicol, Hanover, NH 03755 USA

[7] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03755 USA

来源：

INTERNATIONAL JOURNAL OF COLORECTAL DISEASE | 2009年 / 24卷 / 01期

关键词：

Cytokine; Growth factor; Interleukin; Pancreatic cancer; Metastatic spread; RECEPTOR-ALPHA CHAIN; PSEUDOMONAS EXOTOXIN; CELL-ADHESION; IL-13; CYTOKINE; INSULIN; PROLIFERATION; PROTEIN; SUPERFAMILY; INVOLVEMENT;

D O I：

10.1007/s00384-008-0550-9

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Background and aims Interleukin-13 (IL-13) is an anti-inflammatory cytokine produced in cells of hematopoetic origin. It is not known whether pancreatic cancer cells produce IL-13 or whether IL-13 can modulate pancreatic cancer cell growth and influence the frequency of lymph node metastases. Materials and methods Cell growth and signaling were analyzed by cell counting, colorimetric proliferation assays, fluorescent-activated cell sorting, and in vitro kinase activity assays. IL-13 expression and secretion were determined by Northern blot analysis and enzyme-linked immunosorbent assay, respectively. Localization of IL-13 and its transmembrane receptor (IL-4R) in primary pancreatic ductal adenocarcinoma (PDAC) was characterized by immunohistochemistry. Results IL-13 enhanced the growth of ASPC-1, CAPAN-1, and COLO-357 cells. This was associated with enhanced p44/42 mitogen-activated protein kinase (MAPK) phoshorylation. In contrast to p44/42 MAPK, phosphatidylinositol 3-kinase activity was also induced in IL-13-unresponsive MIA PaCa-2, PANC-1, and T3M4 cells. All cells expressed and secreted IL-13. Neutralizing IL-13 antibodies inhibited the growth of ASPC-1 and CAPAN-1 cells. Immunohistochemical analysis of resected primary ductal adenocarcinoma specimens revealed high levels of IL-13 in 30 of 70 cases and its transmembrane receptor ( IL-4R) in 28 of 70 cases, respectively. Fifteen of 16 specimens (94%) exhibiting high IL-13 and IL-4R coexpression had lymph node metastases, while only 30 of the remaining 54 samples (56%) had positive lymph nodes (p=0.0134). Conclusion IL-13 can act as an autocrine growth factor in PDAC. Endogenous expression of IL-13 in conjunction with IL-4R in the cancer cells seems to facilitate lymph node metastasis.

引用

页码：57 / 67

页数：11

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