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Related Concept Videos

Somatic to iPS Cell Reprogramming01:29

Somatic to iPS Cell Reprogramming

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Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012...
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Adipocytes reprogram prostate cancer stem cell machinery.

Fabrizio Fontana1, Martina Anselmi2, Patrizia Limonta2

  • 1Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy. fabrizio.fontana@unimi.it.

Journal of Cell Communication and Signaling
|March 20, 2023
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Summary

Obesity increases prostate cancer (PCa) risk. Adipose tissue signals can reprogram PCa cells, enhancing their stemness, invasion, and chemoresistance, thus promoting cancer aggressiveness.

Keywords:
AdipocytesCancer stem cellsChemoresistanceEMTMetastasisObesityProstate cancer

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Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Obesity is a known risk factor for prostate cancer (PCa).
  • The interaction between adipose tissue and PCa cells is not fully understood.
  • Understanding this crosstalk is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate how adipocyte-secreted factors influence PCa cell behavior.
  • To determine the impact of adipocyte conditioned media on PCa stemness, aggressiveness, and chemoresistance.
  • To elucidate the mechanisms underlying the pro-tumorigenic effects of adipose tissue in PCa.

Main Methods:

  • Utilized 3T3-L1 adipocyte conditioned media (CM).
  • Exposed PC3 and DU145 PCa cell lines to CM.
  • Assessed changes in sphere formation, stem cell marker expression (CD133, CD44), epithelial-to-mesenchymal transition (EMT), invasion, anoikis resistance, MMP production, and chemoresistance to docetaxel and cabazitaxel.

Main Results:

  • Adipocyte CM treatment enhanced PCa cell sphere formation and expression of CD133 and CD44, indicating increased stemness.
  • PCa cells exposed to CM exhibited partial EMT, characterized by altered E-/N-cadherin expression and Snail upregulation.
  • These phenotypic changes correlated with increased tumor clonogenic activity, survival, invasion, anoikis resistance, MMP production, and significant chemoresistance to standard therapies.

Conclusions:

  • Adipose tissue actively contributes to prostate cancer progression by reprogramming cancer stem cell (CSC) machinery.
  • Adipocytes can induce stem-like properties and mesenchymal traits in PCa cells, leading to increased tumorigenicity, invasion, and chemoresistance.
  • Targeting the adipose-cancer crosstalk may offer novel therapeutic strategies for managing aggressive prostate cancer.