How to rejuvenate the prostate damaged by cancer

Liu, Alvin Y.*

Department of Urology, Institute for Stem Cells and Regenerative Medicine, University of Washington, Seattle, WA, USA

*Correspondence to: Alvin Y. Liu, PhD, aliu@uw.edu.

Abstract

Prostate cancer causes damage to the stromal compartment of smooth muscle cells. These cells control epithelial differentiation through secreted signaling factors and cell contact in development as well as renewal and repair. Stromal cells are depleted by programmed cell death induced by the cancer-secreted anterior gradient 2 protein. In their place, a less differentiated version of cancer-associated stromal cells, which are functionally defective, emerge. Without proper stromal influence, cancer cells can become dedifferentiated to more stem-like with expression of stem cell transcription factors. The importance of identified secreted stromal factors is shown by their induction of cancer cell differentiation with down-regulation of stem cell transcription factors. To maintain prostate function, stromal cells are generated ex vivo through stromal induced differentiation of patient-derived induced pluripotent stem cells. These are then injected into the prostate to restore the pool of stromal cells.

让因癌症受损的前列腺恢复活力： 诱导多能干细胞进行基质诱导分化

摘要

前列腺癌会对平滑肌细胞的基质区造成损伤。这些细胞在发育、更新和修复过程中通过分泌信号因子和细胞接触控制上皮细胞的分化。由癌症分泌的前梯度蛋白2诱导的程序性细胞死亡会消耗掉基质细胞。取而代之的是分化程度较低的癌症相关基质细胞，它们在功能上存在缺陷。如果没有适当的基质影响，癌细胞会随着干细胞转录因子的表达而发生去分化，变得更像干细胞。已确定的分泌型基质因子的重要性体现在它们通过下调干细胞转录因子诱导癌细胞分化。为维持前列腺功能，通过对患者衍生的诱导多能干细胞进行基质诱导分化，在体外生成基质细胞。然后将这些细胞注入前列腺，以恢复基质细胞池。