Department of Internal Medicine, University of Pisa, Italy.
Curr Pharm Biotechnol. 2011 Feb 1;12(2):196-205. doi: 10.2174/138920111794295657.
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.
原发乳腺癌组织中约有 20%的细胞能够在非肥胖型糖尿病严重联合免疫缺陷（NOD/SCID）免疫缺陷小鼠中形成可触及的肿瘤。所有致瘤细胞均来源于正常乳腺干细胞。人类乳腺干细胞对致癌突变敏感，在小鼠模型中与乳腺癌干细胞（BrCSC）具有相似性。致瘤性、侵袭性、进展和转移是 BrCSC 的进一步特性，可能取决于其 CD44+/CD24-表型。局部侵袭和肿瘤转移似乎通过上皮间质转化（EMT）程序得到促进。该程序可能通过稳定的遗传改变或通过癌细胞暴露于周围微环境中存在的因子，或通过 EMT 诱导转录因子的上调而被重新激活。癌细胞对治疗产生耐药性的一个主要解释是，残留肿瘤中具有致瘤潜能的罕见亚群细胞天生对治疗具有耐药性。与该假说一致，在人类乳腺癌中，具有 CD44(high)/CD24(low)细胞表面标志物特征的肿瘤起始性癌症细胞亚群比分化程度更高的乳腺癌细胞更能抵抗癌症治疗（化疗、激素和放疗）。CSC 对化疗、激素治疗和放疗的耐药性的原因也已经被研究，这为癌症治疗开辟了新的前景。
