Stem Cells: Their Role in Breast Cancer Development and Resistance to Treatment

Abstract

About 20% of the total cells from primary breast tumors could generate palpable tumors in non-obese diabetic severe combined immunodeficient (NOD/SCID) immunocompromised mice. All the tumorigenic cells originate from a normal mammary stem cell. Human mammary stem cells are sensitive to oncogenic mutations and in mouse models they share similarities with breast cancer stem cells (BrCSCs). Tumorigenicity, invasion, progression and metastasization are further BrCSCs properties likely depending on their CD44+/CD24- phenotype. Local invasion and tumor metastasization seem to be facilitated by the epithelial to mesenchymal transition (EMT) program. This program may be reactivated from stable genetic alterations or through exposure of cancer cells to factors present in the surrounding micro-environment, or by an up-regulation of EMT-inducing transcription factors. One main explanation for resistance to treatment by cancer cells is that a rare subpopulation of cells in residual tumors with tumorigenic potential is intrinsically resistant to therapy. Consistent with this hypothesis, in human breast tumors, the subpopulation of tumor-initiating cancer cells with CD44(high)/CD24(low) cell surface-marker profile was found more resistant to cancer therapies (chemo, hormone and radiotherapy) than is the major population of more differentiated breast cancer cells. The reasons for CSC resistance to chemotherapy, hormone therapy and radiotherapy also have been examined and they opened new scenarios for cancer therapy.

EpCAM and its potential role in tumor-initiating cells

“…Hence, TICs will be suboptimally affected by conventional approaches 87,88 or even be rather refractory to standard chemotherapy and increase proportionally in numbers upon treatment. [89][90][91] The preference for hypoxic niches makes these cells to inappropriate targets also for angiogenesis inhibitors. Furthermore, the overexpression of detoxifying enzymes or multidrug resistant pumps makes it challenging to target TICs with classical treatments.…”

NK cells control breast cancer and related cancer stem cell hematological spread

“…Moreover, they have been demonstrated to be responsible for the hematological metastatic spread of solid tumors. 8 Therefore, the question of whether cells of the CSC phenotype and tumorigenic potential are common or rare within human cancers has fundamental implications for therapy. 9 If tumorigenic cells are a small minority population, as suggested by the CSC theory, 10,11 improved anticancer therapies may be identified based on their ability to kill CSCs, rather than the bulk population of non-tumorigenic cancer cells.…”

Breast cancer sentinel lymph node and axillary lymphadenectomy: new tools for new challenges

“…Normal stem cells are relatively resistant to chemotherapy owing to mechanisms such as modified expression of anti apoptotic protein families, increases membrane transporter proteins and drugresistance properties [62][63][64][65][66]. Such protein expression in breast cancer cells with tumor growing capacity increases their resistance to conventional chemotherapy regimes.…”