Skip to Content
Merck
  • Therapy-Induced Stromal Senescence Promoting Aggressiveness of Prostate and Ovarian Cancer.

Therapy-Induced Stromal Senescence Promoting Aggressiveness of Prostate and Ovarian Cancer.

Cells (2022-12-24)
Elisa Pardella, Erica Pranzini, Ilaria Nesi, Matteo Parri, Pietro Spatafora, Eugenio Torre, Angela Muccilli, Francesca Castiglione, Massimiliano Fambrini, Flavia Sorbi, Paolo Cirri, Anna Caselli, Martin Puhr, Helmut Klocker, Sergio Serni, Giovanni Raugei, Francesca Magherini, Maria Letizia Taddei
ABSTRACT

Cancer progression is supported by the cross-talk between tumor cells and the surrounding stroma. In this context, senescent cells in the tumor microenvironment contribute to the development of a pro-inflammatory milieu and the acquisition of aggressive traits by cancer cells. Anticancer treatments induce cellular senescence (therapy-induced senescence, TIS) in both tumor and non-cancerous cells, contributing to many detrimental side effects of therapies. Thus, we focused on the effects of chemotherapy on the stromal compartment of prostate and ovarian cancer. We demonstrated that anticancer chemotherapeutics, regardless of their specific mechanism of action, promote a senescent phenotype in stromal fibroblasts, resulting in metabolic alterations and secretion of paracrine factors, sustaining the invasive and clonogenic potential of both prostate and ovarian cancer cells. The clearance of senescent stromal cells, through senolytic drug treatment, reverts the malignant phenotype of tumor cells. The clinical relevance of TIS was validated in ovarian and prostate cancer patients, highlighting increased accumulation of lipofuscin aggregates, a marker of the senescent phenotype, in the stromal compartment of tissues from chemotherapy-treated patients. These data provide new insights into the potential efficacy of combining traditional anticancer strategies with innovative senotherapy to potentiate anticancer treatments and overcome the adverse effects of chemotherapy.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Protease Inhibitor Cocktail, for use with mammalian cell and tissue extracts, DMSO solution
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Phosphatase Inhibitor Cocktail 2, aqueous solution (dark coloration may develop upon storage, which does not affect the activity)
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Bovine Serum Albumin, heat shock fraction, pH 7, ≥98%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
DAPI, for nucleic acid staining
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
VEGF Protein, Human recombinant, The human recombinant VEGF Protein is available in a 10 µg format.
SKU
Pack Size
Availability
Price
Quantity