عزل خلايا ثديية جذعية سرطانية من سرطانات ثدي أولية و تكثيرها و تنميطها : تأسيس نموذج لتقييم الاستجابة لأدوية المعالجة الكيميائية

Abstract EN

Background: Recent years have witnessed mounting interest in cancer stem cells (CSCs) research due to their unique characteristics including self-renewal, promoting metastasis, and resisting radio- and chemotherapies.

High percentage of CSCs in tumor mass is linked to poor prognosis, relapse and metastasis.

These properties have led to recognizing CSCs as promising therapeutic targets and necessitated the establishment of in vitro cellular models that preserve the original characteristics of CSCs, i.e.

their ability to resist chemotherapy, self-renew and differentiate into heterogeneous cellular populations within the tumor mass.

Objective: This study aims at establishing a CSC cellular model that enables evaluating new chemotherapeutics and/or combinatorial therapies of currently existing agents.

Methods: We cultured tumor cells obtained from primary breast tumors of Syrian patients.

This step was followed by isolating single clones by means of serial dilution.

A stem cell population was characterized based on their morphology and surface antigen profile (CD44+/high/CD24-/low) using flow cytometry.

Enriched CSCs were cultured in both adherent and non-adherent conditions.

The viability of CSCs was evaluated after cryopreservation in liquid nitrogen.

Results: In this study, we were able to isolate CSCs from primary breast tumors with approximately 99% purity and well-preserved CSC characteristics including: i) CD44high/CD24-/low profile, ii) ability to form tumorspheres in non-adherent/ultra-low adherence conditions, iii) and ability to resist chemotherapeutic agents in comparison with breast tumor non-stem cells.

Conclusions: Our findings reveal the establishment of a cellular model that preserves the original characteristics of cancer stem cells.

This model may serve as a research tool needed in the efforts to identify the molecular and cellular mechanisms underlying breast cancer resistance to chemo-therapeutics and/or involvement in metastasis.

Furthermore, this model might enable evaluating new therapeutic agents or combinatorial therapeutics and/or enhancing the currently approved treatment strategies.

Comparative assessment of the effectiveness of drug combinations targeting the different heterogeneous tumor cell populations, i.e.

non-stem as well as stem cells, is an obvious application of this model.