Prostate and Breast Cancer Research Group, Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.
Stem Cells. 2011 Aug;29(8):1310-4. doi: 10.1002/stem.668.
Cancer cells are heterogeneous in both their phenotypes and ability to promote tumor growth and spread. Xenografting is used to identify the most highly capable cells of regenerating tumors, referred to as cancer repopulating cells. Because prostate cancers (PCa's) rarely grow as xenografts, indentifying PCa repopulating cells has not been possible. Here, we report improved methods to xenograft localized primary PCa tissues using chimeric grafts with neonatal mouse mesenchyme. Xenograft survival of tumor tissue was significantly increased by neonatal mesenchyme (six of six patients, 66% of grafts, versus four of six patients, 41% of grafts) and doubled the proliferation index of xenografted cancer cells. When applied to isolated PCa cells, neonatal mesenchyme effectively reconstituted PCa's and increased xenograft survival (four of nine patients; 32% of grafts with mesenchyme and 0% without), and supported active cancer cell proliferation. Using this assay, we showed that unfractionated α2β1integrin(hi) and α2β1integrin(lo) cells from primary localized PCa's demonstrated tumor formation at comparable rates, similar to previous reports using metastatic specimens. Thus, this new protocol efficiently established tumors and enabled proliferative expansion of both intact tumor tissue and fractionated cancer cells, providing a bioassay to identify and therapeutically target PCa repopulating cells.
癌细胞在表型和促进肿瘤生长和扩散的能力上存在异质性。异种移植用于鉴定最具再生肿瘤能力的细胞，称为肿瘤再生细胞。由于前列腺癌（PCa）很少作为异种移植物生长，因此无法鉴定 PCa 再生细胞。在这里，我们报告了使用带有新生小鼠间质的嵌合移植物来异种移植局部原发性 PCa 组织的改进方法。新生间质显著增加了肿瘤组织的异种移植存活率（六名患者中的六名，66%的移植物，而六名患者中的四名，41%的移植物），并使异种移植癌细胞的增殖指数增加了一倍。当应用于分离的 PCa 细胞时，新生间质有效地重建了 PCa，并增加了异种移植的存活率（九名患者中的四名；有间质的移植物中 32%，没有间质的移植物中 0%），并支持癌细胞的活跃增殖。使用该测定法，我们表明，来自原发性局部 PCa 的未分级α2β1 整联蛋白（高）和α2β1 整联蛋白（低）细胞以可比的速率形成肿瘤，类似于以前使用转移性标本的报告。因此，这种新方案有效地建立了肿瘤，并使完整肿瘤组织和分级癌细胞的增殖都得到了扩展，为鉴定和治疗性靶向 PCa 再生细胞提供了一种生物测定法。
