Investigation of the Effect of Embryonic Period Cell Secretome-Induced Microenvironment on Cancer Stem Cell Reprogramming
Project no. 32321 · Status: Kapanmış (Yayın bekleniyor) · 2024
Summary
<p>Prostate cancer is one of the most common malignancies in men worldwide, with a high mortality rate in advanced and metastatic cases. Standard approaches such as surgery, radiotherapy, androgen deprivation therapy, and chemotherapy have limited long-term survival. Resistance mechanisms, the suppressive properties of the tumor microenvironment, and the adaptation of cancer stem cells reduce the effectiveness of current treatments. Therefore, the need for new biological strategies to reprogram the tumor phenotype is increasing. Embryonic microenvironments, with their paracrine factors and secretome composition, have the potential to reorganize the proliferation, differentiation, and stem cell-like properties of cancer cells. In this study, the reprogramming effects of four different embryonic secretomes (blastocyst secretome-BCM, trophoblast secretome-HCM, iPSC secretome-HCM, and iPSC-trophoblast combined secretome-I-HCM) were investigated in DU145 prostate cancer cells. Following long-term secretome applications (12 days), cell viability, stem cell ratio, cell cycle, and gene and protein expression were evaluated holistically. Findings showed that secretomes reduced proliferation, increased G0/G1 phase expression, and suppressed the CD44⁺/CD133⁺ stem cell population. Group-specific increases in pluripotency genes were observed, while markers associated with aggressiveness and drug resistance (CD24, ABCG2, MUC1, Ki-67) were decreased. Some of these markers were also supported by immunofluorescence staining.</p><p>In conclusion, our study demonstrates that embryonic secretomes may be strong candidates for novel biotherapeutic approaches in prostate cancer. Isolating the contents of these secretomes (e.g., exosomes, microRNAs, cytokines) and identifying their functional components may lead to future translational applications. Our findings provide important evidence that secretome-based strategies can enable tumor suppressor reprogramming in cancer therapy.</p>