Chemical Therapeutic Program, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231, USA.
Prostate. 2012 Sep 15;72(13):1478-89. doi: 10.1002/pros.22503. Epub 2012 Mar 6.
Recent experimental studies suggest that hierarchical expansion from a minor population of cancer cells with an unlimited self-renewal capacity, termed cancer initiating cells (CICs), drives both lethality and heterogeneity of prostate cancer. Human prostate CICs have been established from only two primary prostate cancer patients, with the remaining established CIC lines being derived from metastatic sites from <10 patients. This suggests that the established CIC lines are significant "outliers" and may not be representative of the prostate CICs seen clinically. Thus, there is an urgent need to develop new approaches to achieve the "routine" establishment of CIC containing lines, particularly derived from primary prostate cancers.
In the present studies, we confirmed that in serum free, high Ca(2+) (i.e., DMEN: F12) growth factor defined (GFD) media plus androgen, a large (n = 10) series of established human prostate cancer cell lines derived from both localized and metastatic sites characteristically self-associate in suspension and grow as unattached spheroids, termed prostaspheres which contain CICs based upon their self-renewal in vitro and tumorigenicity in vivo.
Unfortunately, however, while dissociated single cells from human primary prostate cancer tissues are viable, contain CICs as documented by their ability to take and proliferate as xenografts, and produce prostaspheres when plated with serum free, high Ca(2+) /GFD-media plus androgen onto standard tissue culture flask, these prostasphere do not contain CICs.
The development of reproducibly methods to culture CICs isolated directly from localized cancers is still an urgent unmeet need of the prostate cancer research community.
最近的实验研究表明，具有无限自我更新能力的少量癌细胞（称为癌症起始细胞，CICs）的层次扩展，推动了前列腺癌的致死性和异质性。已经从仅两名原发性前列腺癌患者中建立了人类前列腺 CIC，而其余已建立的 CIC 系则源自<10 名患者的转移部位。这表明已建立的 CIC 系是重要的“异常值”，并且可能不能代表临床上所见的前列腺 CIC。因此，迫切需要开发新方法来实现 CIC 包含系的“常规”建立，特别是从原发性前列腺癌中建立。
在本研究中，我们证实了在无血清、高钙（即 DMEN：F12）生长因子定义（GFD）培养基加雄激素中，大量（n=10）已建立的人前列腺癌细胞系源自局部和转移部位，其特征在于在悬浮液中自我聚集并作为无附着球体生长，称为 prostaspheres，这些球体基于其在体外的自我更新和体内致瘤性包含 CIC。
然而，不幸的是，尽管从人原发性前列腺癌组织中分离的离散单细胞是可行的，包含 CIC，正如其作为异种移植物增殖的能力所证明的那样，并且在无血清、高钙/GFD 培养基加雄激素中接种到标准组织培养瓶时产生 prostaspheres，但是这些 prostasphere 不包含 CIC。
从局部癌症中直接分离培养 CIC 的可重复方法的开发仍然是前列腺癌研究界急需解决的问题。
