研究人员找出肝癌肿瘤变得可见之前的祖细胞

StephenW

          Researchers identify liver cancer progenitor cells before tumors become visible                                                                                                                                                                                                                   
                                   This is a stained liver biopsy micrograph showing hepatocellular carcinoma cells with Mallory bodies (reds and blacks). Credit: University of California - San Diego                                                                                                        For the first time, researchers at the University of California, San Diego School of Medicine have isolated and characterized the progenitor cells that eventually give rise to malignant hepatocellular carcinoma (HCC) tumors – the most common form of liver cancer. The researchers found ways to identify and isolate the HCC progenitor cells (HcPC) long before actual tumors were apparent.
                                                       
                                       
                        Writing in the October 10, 2013 issue of the journal Cell, principal investigator Michael Karin, PhD, Distinguished Professor of Pharmacology and Pathology, and colleagues report that HcPC take form within dysplastic or abnormal lesions often found in damaged or cirrhotic livers. The liver damage can be due to viral infections like hepatitis or from chronic alcohol abuse.
"It was never established whether dysplastic lesions are just a regenerative (healing) response of the liver triggered by tissue damage or are actually pre-malignant lesions that harbor tumor progenitor cells," said study co-author Debanjan Dhar, PhD, a postdoctoral researcher in Karin's lab. "Here we show that HcPC are likely derived from dysplastic lesions, can progress to malignant tumors and further demonstrate that the malignant progression of HcPC to full-blown liver cancer depends upon the microenvironment that surrounds them."
The researchers were able to characterize HcPC based on several biomarkers that distinguish them from normal cells. They also identified cellular signaling pathways activated in HcPC that are critical "to their malignant potential," said Dhar.
The findings may have profound implications for treating HCC which, while relatively rare in the United States compared to other types of cancer, is difficult to diagnose and treat, with poor prognoses for patients. HCC is usually fatal within three to six months of diagnosis, according to National Institutes of Health data. An estimated 30,000 new cases of liver cancer are diagnosed annually in the U.S., predominantly among men. More than 21,600 Americans die from liver cancer each year, a rate that has been rising slowly for several decades. In other parts of the world, HCC is a major cause of cancer-related deaths.
Most cancers are best detected and treated at the earliest possible stage. HCC is problematic because it develops slowly and frequently displays no symptoms. By the time it is detected, said Dhar, it is usually at an advanced stage with no effective therapy.
"Our findings can be translated into both early detection and therapeutic intervention," he said. "Better understanding of HcPC cellular networks will provide us with new and effective therapeutic targets."
For example, the researchers were able to detect "potential" malignant lesions in needle biopsies of a subset of patients infected with the hepatitis C virus, but who hadn't yet developed HCC. Hepatitis C is a major risk factor for HCC development.
Dhar said identifying premalignant lesions in high-risk patients based on HcPC markers would allow for earlier detection and therapeutic interventions. "Furthermore, in future, therapies can be developed to specifically eliminate the HcPC even before a tumor has developed."

StephenW

研究人员找出肝癌肿瘤变得可见之前的祖细胞
这是一个染肝活检显示肝癌细胞的显微镜Mallory小体（红色和黑色） 。信用：美国加州大学 - 圣地亚哥

对于第一次，在美国加州大学圣地亚哥医学院的研究人员分离和特征的祖细胞，最终会导致恶性肝细胞癌（HCC ）肿瘤 - 肝癌的最常见的形式。研究人员发现的方法来识别和隔离肝癌祖细胞（ HCPC ）长，在实际的肿瘤明显。

写在10月10日的Cell杂志上， 2013年的问题，首席研究员迈克尔·卡琳，药理学和病理学博士，特聘教授和他的同事报告说， HCPC内采取的形式往往发现损坏或肝硬化肝脏的发育不良或异常病变。肝损害可能是由于病毒感染，如肝炎或慢性酗酒。

“这是从来没有确定是否只是不典型增生病变组织损伤引发的肝脏再生（愈合）响应，或实际上是癌前病变，心怀祖细胞瘤，说：”研究的共同作者Debanjan达尔博士，博士后研究员在卡琳实验室。 “在这里，我们表明， HCPC可能来自不典型增生病变，可进展为恶性肿瘤，并进一步证明，的恶性进展HCPC ，全面肝癌取决于微环境，围绕着他们。 ”

研究人员已经能够表征基于HCPC的几种生物标志物，他们从正常细胞区分开来。他们还发现细胞信号通路激活HCPC是至关重要的“恶性潜能， ”达尔说。

这一发现可能具有深远的意义，为治疗肝癌，而在美国比较少见，相比其他类型的癌症，是很难诊断和治疗，对患者的预后差。通常是致命的肝癌诊断后三到六个月内，根据国立健康数据。肝癌估计30,000个新病例被确诊，每年在美国，主要是男性。 21,600多名美国人死于肝癌，每年的速度已经缓慢上升了几十年。在世界其他地区，肝癌是癌症相关死亡的一个主要原因。

大多数癌症最好是尽早发现和治疗。肝癌是有问题的，因为它的发展缓慢，并经常不显示症状。的时候它被检测到，达尔说，它通常是在一个先进的阶段，没有有效的治疗。

，“他说： ”我们的研究结果可以被翻译成早期检测和治疗干预。 “更好地了解的HCPC蜂窝网络将为我们提供新的和有效的治疗目标。 ”

例如，研究人员能够检测到“潜在的”恶性病变穿刺活检患者感染丙型肝炎病毒的一个子集，但尚未开发肝癌。丙型肝炎是一种主要的危险因素，肝癌发展。

达尔说，将允许在高风险患者基于HCPC标记识别癌前病变早期检测和治疗干预。 “此外，在未来，治疗可以开发甚至在肿瘤发展专门消除HCPC的。