Platelet-derived growth factor B induces senescence and transformation in normal human fibroblasts

David Vindrieux1, Baptiste Gras, Merce Garcia-Belinchon

  • 1Inserm U1052, Centre de Recherche en Cancérologie de Lyon, Lyon, F-69000, France.

Aging
|August 13, 2013
PubMed

Insights

Platelet-derived growth factor B (PDGFB) can induce both senescence and cellular transformation in normal cells. This p53-dependent senescence response limits PDGFB

Area of Science:

  • Cellular biology
  • Oncology
  • Molecular mechanisms of cancer

Background:

  • Cellular senescence is a tumor suppressive mechanism triggered by oncogenic signals.
  • The role of mitogenic growth factors, like Platelet-derived growth factor B (PDGFB), in inducing senescence is not well understood.
  • Oncogene-induced senescence (OIS) is a known phenomenon, but the impact of growth factors on senescence requires further investigation.

Purpose of the Study:

  • To investigate the effect of Platelet-derived growth factor B (PDGFB) on cellular senescence in normal human dermal fibroblasts.
  • To determine the relationship between PDGFB-induced senescence and cellular transformation.
  • To elucidate the role of the p53 pathway in PDGFB-mediated senescence.

Main Methods:

  • Culturing normal human dermal fibroblasts.
  • Inducing Platelet-derived growth factor B (PDGFB) expression.
  • Assessing cellular senescence and transformation markers.
  • Inhibiting the p53 signaling pathway.

Main Results:

  • PDGFB expression induced a complex response, leading to both senescence and cellular transformation in the same cell population.
  • Sustained passage of cells indicated that transformed cells eventually entered a senescent state.
  • Inhibition of the p53 pathway abolished PDGFB-induced senescence and significantly increased cellular transformation.
  • Human dermatofibrosarcoma protuberans, tumors with constitutive PDGFB, exhibited senescence hallmarks.

Conclusions:

  • PDGFB exhibits a limited capacity to induce cellular senescence.
  • The p53 pathway is crucial for mediating PDGFB-induced senescence.
  • This partial senescence may attenuate but not eliminate the transforming potential of PDGFB.
  • Findings are supported by observations in PDGFB-driven skin tumors, suggesting a role for senescence in modulating tumor aggressiveness.

Related Concept Videos

TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
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...
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...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
Replicative Cell Senescence02:15

Replicative Cell Senescence

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds the telomeric...