Interleukin-4 receptor expression and growth inhibition of gastro-intestinal carcinoma cells by IL-4

Morisaki, T.; Katano, Motonobu; Uchiyama, Ayako; Torisu, Motomichi

doi:10.1016/0928-4680(94)90814-1

Cited by 17 publications

(21 citation statements)

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“…In cancer cells, IL-4 often promotes proliferation, metastasis, and expression of anti-apoptotic genes (13)(14)(15)(16). On the other hand, we and others have shown that IL-4 directly inhibits growth of several human cancer cell lines including those derived from breast, gastric, colon, and renal cancers (17)(18)(19)(20)(21)(22). In addition, apoptosis can be induced or suppressed by IL-4: IL-4 induced apoptosis in certain cell types, including breast and liver cancer cells, hepatocytes, endothelial cells, monocytes, and developing mast cells (23)(24)(25)(26), whereas it increased resistance to apoptosis in mouse fibrosarcoma cell lines and STAT6-high human cancer cell lines such as HT-29 and ZR-75-1 (16,27).…”

Section: Interleukin (Il)mentioning

confidence: 99%

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Interleukin-4 Induces Senescence in Human Renal Carcinoma Cell Lines through STAT6 and p38 MAPK

Kim

et al. 2013

Journal of Biological Chemistry

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Background: IL-4 can directly inhibit growth of several tumor cell types, but the molecular mechanism is not known. Results: IL-4 induces senescence by increasing p21 WAF1/CIP1 expression through STAT6 and p38 MAPK. Conclusion: STAT6 and p38 MAPK play important roles in senescence induction by IL-4. Significance: This is the first report of cellular senescence induction by IL-4 and the responsible mechanism.

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Section: Interleukin (Il)mentioning

confidence: 99%

“…inhibits cell growth in several human cancer cell lines with or without inducing apoptosis (17)(18)(19)(20)(21)(22)28). To evaluate the effects of IL-4 on the growth of human RCC cells, Caki-1, A498, and 786-O cells were exposed to 1-10 ng/ml of IL-4 for 24 h, and cell proliferation was measured by a […”

Section: Il-4 Inhibits Growth Of Human Rcc Cells-il-4mentioning

confidence: 99%

Interleukin-4 Induces Senescence in Human Renal Carcinoma Cell Lines through STAT6 and p38 MAPK

Kim

et al. 2013

Journal of Biological Chemistry

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“…The significance of IL-4Rs expression in pancreatic cancer and other solid tumours is still unknown. In contrast to its growth stimulatory effect on lymphocytes, IL-4 has been shown to have a modest but direct inhibitory effect on the growth of tumour cells of haematopoietic and nonhaematopoietic origin in vitro and in vivo, including those derived from human melanoma, non-Hodgkin's malignant B-lymphoma, and colon, renal, gastric, and breast carcinoma (Defrance et al, 1992;Gallagher and Zaloom, 1992;Morisaki et al, 1992;Toi et al, 1992, Obiri et al, 1993.…”

mentioning

confidence: 99%

Interleukin-4 enhances proliferation of human pancreatic cancer cells: evidence for autocrine and paracrine actions

et al. 2005

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Interleukin-4 (IL-4) is an immunomodulatory cytokine, which can inhibit the growth of tumour cells. Pancreatic cancer cells and tissues express high levels of IL-4 receptors. The aim of this study was to characterise the effects of IL-4 on the growth and signalling pathways of pancreatic cancer cells. Cell growth was determined by cell counting and MTT assays in association with fluorescenceactivated cell sorter analysis, IL-4 expression using ELISA and real-time PCR techniques, and signal transduction using immunoprecipitation or immunoblot analysis. We now report for the first time that IL-4 significantly enhanced the growth of five out of six cultured pancreatic cancer cell lines in a dose-dependent manner in association with an increased fraction of cells in Sphase. Surprisingly, all six cell lines expressed endogenous IL-4, and IL-4 was detectable in the supernatant. Incubating cells with neutralising IL-4 antibodies resulted in a significant inhibition of basal growth in three cell lines, including IL-4-unresponsive MIA PaCa-2 cells, which however expressed the highest endogenous IL-4 levels. Interleukin-4 enhanced activity of MAPK, Akt-1, and Stat3 in IL-4-responsive, but not in IL-4-unresponsive MIA PaCa-2 cells; however, IL-4 enhanced tyrosine phosphorylation of insulin receptor substrate-1 and -2 in all cell lines. Our results demonstrate for the first time that pancreatic cancer cells produce IL-4 and that IL-4 can act as a growth factor in pancreatic cancer cells. Together with the observation that neutralising IL-4 antibodies can inhibit the growth of these cells, our results suggest that IL-4 may act as an autocrine growth factor in pancreatic cancer cells and also give rise to the possibility that cancer-derived IL-4 may suppress cancer-directed immunosurveillance in vivo in addition to its growth-promoting effects, thereby facilitating pancreatic tumour growth and metastasis.

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“…Our demonstration that gp200-MR6, which is functionally associated with the IL-4R, is expressed on neoplastic urothelium and other epithelia raises important questions about such possible therapeutic applications of IL-4 (Larche et al, 1988;Mat et al, 1990;Tungekar et al, 1991;Kaklamanis et al, 1992;Mat et al, 1993;Imami et al, 1994 (Totpal et al, 1991;Morisaki et al, 1992Morisaki et al, , 1994Toi et al, 1992;Obiri et al, 1993Obiri et al, , 1994. Clinical studies of certain subsets of breast cancers suggest that cytokines released from host cells infiltrating tumour stroma may act in a paracrine fashion to promote growth of neoplastic cells and that cytotoxic therapy is beneficial because of its immunosuppressive effects (Stewart and Tsai, 1993).…”

Section: Resultsmentioning

confidence: 95%

“…The IL-4 receptor (IL-4R), which comprises the IL-4 binding component (CD124) together with the common y-chain (yc) is expressed by B and T lymphocytes, macrophages and mast cells (Jansen et al, 1990;Russel et al, 1993). Increasingly however its presence is being reported on non-haemopoietic cells such as cell lines derived from melanoma and various epithelial tumours (Morisaki et al, 1992;Toi et al, 1992;Obiri et al, 1993Obiri et al, , 1994.…”

mentioning

confidence: 99%

Bladder carcinomas and normal urothelium universally express gp200-MR6, a molecule functionally associated with the interleukin 4 receptor (CD 124)

Gatter²,

Ma³

1996

Br J Cancer

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Interleukin-4 receptor expression and growth inhibition of gastro-intestinal carcinoma cells by IL-4

Cited by 17 publications

References 0 publications

Interleukin-4 Induces Senescence in Human Renal Carcinoma Cell Lines through STAT6 and p38 MAPK

Interleukin-4 Induces Senescence in Human Renal Carcinoma Cell Lines through STAT6 and p38 MAPK

Interleukin-4 enhances proliferation of human pancreatic cancer cells: evidence for autocrine and paracrine actions

Bladder carcinomas and normal urothelium universally express gp200-MR6, a molecule functionally associated with the interleukin 4 receptor (CD 124)

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