Presence Of Breast Cancer Stem Cells Research Articles

Unraveling the Potential of miRNAs from CSCs as an Emerging Clinical Tool for Breast Cancer Diagnosis and Prognosis.

Breast cancer (BC) is the most diagnosed cancer in women and the second most common cancer globally. Significant advances in BC research have led to improved early detection and effective therapies. One of the key challenges in BC is the presence of BC stem cells (BCSCs). This small subpopulation within the tumor possesses unique characteristics, including tumor-initiating capabilities, contributes to treatment resistance, and plays a role in cancer recurrence and metastasis. In recent years, microRNAs (miRNAs) have emerged as potential regulators of BCSCs, which can modulate gene expression and influence cellular processes like BCSCs' self-renewal, differentiation, and tumor-promoting pathways. Understanding the miRNA signatures of BCSCs holds great promise for improving BC diagnosis and prognosis. By targeting BCSCs and their associated miRNAs, researchers aim to develop more effective and personalized treatment strategies that may offer better outcomes for BC patients, minimizing tumor recurrence and metastasis. In conclusion, the investigation of miRNAs as regulators of BCSCs opens new directions for advancing BC research through the use of bioinformatics and the development of innovative therapeutic approaches. This review summarizes the most recent and innovative studies and clinical trials on the role of BCSCs miRNAs as potential tools for early diagnosis, prognosis, and resistance.

Evaluation of chemotherapy and P2Et extract combination in ex-vivo derived tumor mammospheres from breast cancer patients

The main cause of death by cancer is metastasis rather than local complications of primary tumors. Recent studies suggest that breast cancer stem cells (BCSCs), retains the ability to self-renew and differentiate to repopulate the entire tumor, also, they have been associated with resistance to chemotherapy and tumor recurrence, even after tumor resection. Chemotherapy has been implicated in the induction of resistant phenotypes with highly metastatic potential. Naturally occurring compounds, especially phytochemicals such as P2Et, can target different populations of cancer cells as well as BCSC, favoring the activation of immune response via immunogenic tumor death. Here, we evaluated the presence of BCSC as well as markers related to drug resistance in tumors obtained from 78 patients who had received (or not) chemotherapy before surgery. We evaluated the ex vivo response of patient tumor-derived organoids (or mammospheres) to chemotherapy alone or in combination with P2Et. A xenotransplant model engrafted with MDA-MB-468 was used to evaluate in vivo the activity of P2Et, in this model P2Et delay tumor growth. We show that patients with luminal and TNBC, and those who received neoadjuvant therapy before surgery have a higher frequency of BCSC. Further, the treatment with P2Et in mammospheres and human breast cancer cell lines improve the in vitro tumor death and decrease its viability and proliferation together with the release of immunogenic signals. P2Et could be a good co-adjuvant in antitumor therapy in patients, retarding the tumor growth by enabling the activation of the immune response.

Abstract 2002: Ganoderma lucidum extract (GLE) reduces stem cell markers in triple-negative breast cancer models via STAT3 regulation

Abstract Triple-negative breast cancer (TNBC) is a subtype of cancer described by the lack of estrogen receptor, progestogen receptor, and HER2 receptor. It accounts for approximately 15-20% of all breast cancer (BC) cases worldwide. TNBC aggressiveness might be explained by the presence of BC stem cells (BCSCs), which are a subpopulation of cancer cells involved in tumor initiation, metastasis, and therapy resistance. Interestingly, the signal transducer and activator of transcription 3 (STAT3) participates in the development and progression of BCSCs, but its role in TNBC progression remains unclear. Moreover, BCSCs can be identified by the CD44+/CD24- and ALDH+ phenotype, which correlates with a worse prognosis in TNBC patients. Furthermore, CSCs can be characterized based on the expression of transcription factors involved in stemness (Nanog, Sox2, and Oct4A), where activation of STAT3 leads to enhanced Nanog, Oct4 and Sox2 expression. Importantly, a major challenge arises to develop nontoxic targeted therapies to improve the outcome of TNBC patients. In this regard, our laboratory investigates the role of Ganoderma lucidum extract (GLE), a medicinal mushroom commonly used in complementary and alternative medicine. We hypothesize that GLE will decrease stem cell properties via STAT3 regulation in TNBC cells. Our in vitro results demonstrate that GLE significantly downregulates STAT3 and JAK2 in SUM-149 and MDA-MB-231, TNBC cell lines. In addition, GLE significantly decreases the secretion of IL-6 at 24hr in MDAMB231 cells. Further flow cytometry results show that GLE significantly decreases the CD44+/CD24- population at 24hr and 72hr in MDA-MB-231 cells. In this regard, GLE significantly decreases the expression of ALDH at 24hr and 72hr in MDAMB231 cells. Moreover, GLE decreases the expression of Nanog at 24hr, and all three transcription factors at 72hr. Additionally, our in vivo studies demonstrate that GLE significantly decreases tumor volume of mice injected with CD44+/CD24- sorted cells of the MDA-MB-231 cell line. Finally, tumor weight of GLE treated mice was marginally significantly lower (p=0.053) compared to vehicle. We can conclude that GLE decreases stemness of TNBC via STAT3 regulation. Citation Format: Tiffany J. Rios, Alicia Marti, Gabriela Ortiz, Michelle M. Martínez-Montemayor. Ganoderma lucidum extract (GLE) reduces stem cell markers in triple-negative breast cancer models via STAT3 regulation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2002.