Apoptosis resistance in epithelial tumors is mediated by tumor-cell-derived interleukin-4

Giorgio Stassi, Cristoforo Di Bernardo, Patrizia Cammareri, Flora Iovino, Anna Barbara Di Stefano, Matilde Todaro, Antonino Agrusa, Walczak, Condorelli, Maria Giovanna Francipane, Mileidys Perez Alea, Ylenia Lombardo

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129 Citazioni (Scopus)

Abstract

We investigated the mechanisms involved in the resistance to cell death observed in epithelial cancers. Here, we identify thatprimary epithelial cancer cells from colon, breast and lung carcinomas express high levels of the antiapoptotic proteins PED,cFLIP, Bcl-xL and Bcl-2. These cancer cells produced interleukin-4 (IL-4), which amplified the expression levels of theseantiapoptotic proteins and prevented cell death induced upon exposure to TRAIL or other drug agents. IL-4 blockade resulted ina significant decrease in the growth rate of epithelial cancer cells and sensitized them, both in vitro and in vivo, to apoptosisinduction by TRAIL and chemotherapy via downregulation of the antiapoptotic factors PED, cFLIP, Bcl-xL and Bcl-2.Furthermore, we provide evidence that exogenous IL-4 was able to upregulate the expression levels of these antiapoptoticproteins and potently stabilized the growth of normal epithelial cells rendering them apoptosis resistant. In conclusion, IL-4 actsas an autocrine survival factor in epithelial cells. Our results indicate that inhibition of IL-4/IL-4R signaling may serve as a noveltreatment for epithelial cancers.
Lingua originaleEnglish
pagine (da-a)762-772
Numero di pagine11
RivistaCell Death and Differentiation
Volume15
Stato di pubblicazionePublished - 2008

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Interleukin-4
Apoptosis
Epithelial Cells
Neoplasms
Cell Death
Growth
Colonic Neoplasms
Lung Neoplasms
Proteins
Up-Regulation
Down-Regulation
Breast Neoplasms
Drug Therapy
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cita questo

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title = "Apoptosis resistance in epithelial tumors is mediated by tumor-cell-derived interleukin-4",
abstract = "We investigated the mechanisms involved in the resistance to cell death observed in epithelial cancers. Here, we identify thatprimary epithelial cancer cells from colon, breast and lung carcinomas express high levels of the antiapoptotic proteins PED,cFLIP, Bcl-xL and Bcl-2. These cancer cells produced interleukin-4 (IL-4), which amplified the expression levels of theseantiapoptotic proteins and prevented cell death induced upon exposure to TRAIL or other drug agents. IL-4 blockade resulted ina significant decrease in the growth rate of epithelial cancer cells and sensitized them, both in vitro and in vivo, to apoptosisinduction by TRAIL and chemotherapy via downregulation of the antiapoptotic factors PED, cFLIP, Bcl-xL and Bcl-2.Furthermore, we provide evidence that exogenous IL-4 was able to upregulate the expression levels of these antiapoptoticproteins and potently stabilized the growth of normal epithelial cells rendering them apoptosis resistant. In conclusion, IL-4 actsas an autocrine survival factor in epithelial cells. Our results indicate that inhibition of IL-4/IL-4R signaling may serve as a noveltreatment for epithelial cancers.",
author = "Giorgio Stassi and {Di Bernardo}, Cristoforo and Patrizia Cammareri and Flora Iovino and {Di Stefano}, {Anna Barbara} and Matilde Todaro and Antonino Agrusa and Walczak and Condorelli and Francipane, {Maria Giovanna} and {Perez Alea}, Mileidys and Ylenia Lombardo",
year = "2008",
language = "English",
volume = "15",
pages = "762--772",
journal = "Cell Death and Differentiation",
issn = "1350-9047",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Apoptosis resistance in epithelial tumors is mediated by tumor-cell-derived interleukin-4

AU - Stassi, Giorgio

AU - Di Bernardo, Cristoforo

AU - Cammareri, Patrizia

AU - Iovino, Flora

AU - Di Stefano, Anna Barbara

AU - Todaro, Matilde

AU - Agrusa, Antonino

AU - Walczak, null

AU - Condorelli, null

AU - Francipane, Maria Giovanna

AU - Perez Alea, Mileidys

AU - Lombardo, Ylenia

PY - 2008

Y1 - 2008

N2 - We investigated the mechanisms involved in the resistance to cell death observed in epithelial cancers. Here, we identify thatprimary epithelial cancer cells from colon, breast and lung carcinomas express high levels of the antiapoptotic proteins PED,cFLIP, Bcl-xL and Bcl-2. These cancer cells produced interleukin-4 (IL-4), which amplified the expression levels of theseantiapoptotic proteins and prevented cell death induced upon exposure to TRAIL or other drug agents. IL-4 blockade resulted ina significant decrease in the growth rate of epithelial cancer cells and sensitized them, both in vitro and in vivo, to apoptosisinduction by TRAIL and chemotherapy via downregulation of the antiapoptotic factors PED, cFLIP, Bcl-xL and Bcl-2.Furthermore, we provide evidence that exogenous IL-4 was able to upregulate the expression levels of these antiapoptoticproteins and potently stabilized the growth of normal epithelial cells rendering them apoptosis resistant. In conclusion, IL-4 actsas an autocrine survival factor in epithelial cells. Our results indicate that inhibition of IL-4/IL-4R signaling may serve as a noveltreatment for epithelial cancers.

AB - We investigated the mechanisms involved in the resistance to cell death observed in epithelial cancers. Here, we identify thatprimary epithelial cancer cells from colon, breast and lung carcinomas express high levels of the antiapoptotic proteins PED,cFLIP, Bcl-xL and Bcl-2. These cancer cells produced interleukin-4 (IL-4), which amplified the expression levels of theseantiapoptotic proteins and prevented cell death induced upon exposure to TRAIL or other drug agents. IL-4 blockade resulted ina significant decrease in the growth rate of epithelial cancer cells and sensitized them, both in vitro and in vivo, to apoptosisinduction by TRAIL and chemotherapy via downregulation of the antiapoptotic factors PED, cFLIP, Bcl-xL and Bcl-2.Furthermore, we provide evidence that exogenous IL-4 was able to upregulate the expression levels of these antiapoptoticproteins and potently stabilized the growth of normal epithelial cells rendering them apoptosis resistant. In conclusion, IL-4 actsas an autocrine survival factor in epithelial cells. Our results indicate that inhibition of IL-4/IL-4R signaling may serve as a noveltreatment for epithelial cancers.

UR - http://hdl.handle.net/10447/60168

M3 - Article

VL - 15

SP - 762

EP - 772

JO - Cell Death and Differentiation

JF - Cell Death and Differentiation

SN - 1350-9047

ER -