Basal Cell Proliferation Induced by Chlormadinone Acetate Suggests Stem Cell Transformation of Prostatic Cells

Abstract

Introduction and Objective: Epithelial to Mesenchymal transition (EMT) at the first hormonal therapy is thought to play an essential role in obtaining castrate resistance for hormone naïve prostate cancer. So we studied EMT of prostatic cells after exposing various hormonal agents using transurethral resection (TUR) specimens. Patients and Methods: TUR specimens without hormonal use (4 cases), specimens after three weeks of chlormadinone acetate (CMA) (9 cases), specimens after average six months of dutasteride (3 cases), and specimens two weeks after initial use of degarelix (3 cases) were studied using HE and immunohistochemical staining with prostate specific antigen (PSA), prostatic stem cell markers such as CD44, CD117, CD133 and Vimentin. Results: Specimens treated with CMA showed acinar dilatation and atrophy of glandular cells. Specimens treated with dutasteride showed marked decrease of gland and specimens treated with degarelix showed decrease of glandular cells. PSA was stained all of the prostatic glandular cells in all specimens. CD44 was stained at basal cells in normal prostatic tissue without hormones, however in hormone treated specimens, basal cells elongate and some glandular cells were also stained by CD44, especially in CMA treated specimens. Only small numbers of infiltrating cells in interstitial tissue positively stained with CD 117 and CD 133 in all specimens. Vimentin was stained in all mesenchymal interstitial cells. Conclusion: Elongation of basal cells and increased sensitivity to CD44 in glandular cells, especially treated with CMA, were thought to the result of EMT of prostatic glandular cells.

Basal Cell Hyperplasia Observed at Biopsy Specimens after HIFU Therapy: Implication of Stemness for Organ Regeneration

“…Although the exact mechanism of forming BCH was unclear, the proliferation of basal cell differentiated stem cells may trigger the initiation of cancer or hyperplastic formation [11] [12] [13]. The apoptosis of luminal cells is also reported as a trigger of proliferation induced by inflammation or change of hormonal environment [14]. The stemness property of these basal cells is thought to be very important for tissue regeneration [15].…”

Castration-Synchronized Upfront Docetaxel for metastatic Hormone Sensitive Prostate Cancer considering Epithelial to Mesenchymal Transition

“…10 Three weeks administration of chlormadinone acetate (synthetic progesterone) (CMA) proved to induce stem cell transformation of prostatic cells by basal cell proliferation (Figure 1). 11 The proposed mechanism of this phenomena is indicated in Figure 2. Jaworska and Szliszka reported that cancer cells re-sensitized to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) by docetaxel when cancer stem cells reduce TRAIL function for PC3 prostate cancer cells.…”