Department of Surgery, Royal College of Surgeons in Ireland; Dublin, Ireland.
J Exp Clin Cancer Res. 2011 Apr 26;30(1):45. doi: 10.1186/1756-9966-30-45.
Many factors influence breast cancer progression, including the ability of progenitor cells to sustain or increase net tumour cell numbers. Our aim was to define whether alterations in putative progenitor populations could predict clinicopathological factors of prognostic importance for cancer progression.
Primary cultures were established from human breast tumour and adjacent non-tumour tissue. Putative progenitor cell populations were isolated based on co-expression or concomitant absence of the epithelial and myoepithelial markers EPCAM and CALLA respectively.
Significant reductions in cellular senescence were observed in tumour versus non-tumour cultures, accompanied by a stepwise increase in proliferation:senescence ratios. A novel correlation between tumour aggressiveness and an imbalance of putative progenitor subpopulations was also observed. Specifically, an increased double-negative (DN) to double-positive (DP) ratio distinguished aggressive tumours of high grade, estrogen receptor-negativity or HER2-positivity. The DN:DP ratio was also higher in malignant MDA-MB-231 cells relative to non-tumorigenic MCF-10A cells. Ultrastructural analysis of the DN subpopulation in an invasive tumour culture revealed enrichment in lipofuscin bodies, markers of ageing or senescent cells.
Our results suggest that an imbalance in tumour progenitor subpopulations imbalances the functional relationship between proliferation and senescence, creating a microenvironment favouring tumour progression.
许多因素会影响乳腺癌的进展，包括祖细胞维持或增加净肿瘤细胞数量的能力。我们的目的是确定祖细胞群体的改变是否可以预测癌症进展中具有重要预后意义的临床病理因素。
从人乳腺癌肿瘤和相邻非肿瘤组织中建立原代培养物。基于上皮和肌上皮标志物 EPCAM 和 CALLA 的共表达或同时缺失，分别分离假定的祖细胞群体。
与非肿瘤培养物相比，肿瘤培养物中细胞衰老明显减少，同时增殖：衰老比率逐渐增加。还观察到肿瘤侵袭性与假定祖细胞亚群失衡之间的新相关性。具体而言，双阴性 (DN) 到双阳性 (DP) 的比值增加可区分高级别、雌激素受体阴性或 HER2 阳性的侵袭性肿瘤。DN:DP 比值在恶性 MDA-MB-231 细胞中也高于非致瘤性 MCF-10A 细胞。在侵袭性肿瘤培养物中对 DN 亚群进行超微结构分析发现富含脂褐素体，这是衰老或衰老细胞的标志物。
我们的研究结果表明，肿瘤祖细胞亚群的失衡破坏了增殖和衰老之间的功能关系，从而创造了有利于肿瘤进展的微环境。
