Related Experiment Video

Updated: Jun 10, 2026

Fluorescence Microscopy for ATP Internalization Mediated by Macropinocytosis in Human Tumor Cells and Tumor-xenografted Mice
08:31

Fluorescence Microscopy for ATP Internalization Mediated by Macropinocytosis in Human Tumor Cells and Tumor-xenografted Mice

Published on: June 30, 2021

ATP confers tumorigenic properties to dendritic cells by inducing amphiregulin secretion

Nathalie Bles1, Larissa Di Pietrantonio, Jean-Marie Boeynaems

  • 1Institute of Interdisciplinary Research, Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, 808 Route de Lennik, Brussels, Belgium.

Blood
|July 24, 2010
PubMed

Insights

Adenosine triphosphate (ATP) signaling in dendritic cells (DCs) promotes tumor growth by stimulating amphiregulin (AREG) release. Targeting ATP receptors or AREG may offer new cancer therapies.

Area of Science:

  • Immunology
  • Cell Biology
  • Cancer Research

Background:

  • Adenosine triphosphate (ATP) acts as a danger signal with proinflammatory effects.
  • ATP can induce semi-maturation of dendritic cells (DCs), potentially influencing immune tolerance.
  • Dendritic cells play a crucial role in initiating and regulating immune responses.

Purpose of the Study:

  • To investigate the molecular targets of ATP signaling in dendritic cells.
  • To determine if ATP-stimulated DCs can influence tumor cell growth.
  • To explore the therapeutic potential of targeting ATP-DC-tumor cell interactions.

Main Methods:

  • Gene profiling of DCs treated with ATPγS (a stable ATP analog).
  • Measurement of amphiregulin (AREG) release from human and mouse DCs upon purinergic receptor activation.
  • In vitro and in vivo experiments assessing the effect of DC supernatants and stimulated DCs on tumor cell growth.
  • Use of anti-AREG blocking antibodies to neutralize AREG's effects.

Main Results:

  • Epidermal growth factor receptor ligands were identified as target genes of ATPγS in DCs, with amphiregulin (AREG) being highly upregulated.
  • Activated DCs released AREG via purinergic receptors (P2Y(11) and A(2B)).
  • Supernatants from LPS+ATPγS-stimulated DCs promoted smooth muscle cell and Lewis Lung Carcinoma (LLC) cell growth in vitro and increased tumor weight in vivo.
  • Anti-AREG antibody treatment blocked the pro-tumorigenic effects of DC supernatants.

Conclusions:

  • Dendritic cells are a novel source of amphiregulin (AREG).
  • Tumor-released ATP may promote tumorigenesis by stimulating AREG secretion from DCs.
  • Targeting purinergic receptors on DCs or using anti-AREG antibodies presents potential therapeutic strategies for cancer treatment.

More Related Videos

Preparation of Tumor Antigen-loaded Mature Dendritic Cells for Immunotherapy08:40

Preparation of Tumor Antigen-loaded Mature Dendritic Cells for Immunotherapy

Published on: August 1, 2013

Tumor Allotransplantation in Drosophila melanogaster with a Programmable Auto-Nanoliter Injector05:06

Tumor Allotransplantation in Drosophila melanogaster with a Programmable Auto-Nanoliter Injector

Published on: February 2, 2021

Related Concept Videos

The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...